Cell Host & Microbe

Review

Phytopathogen Effectors Subverting Host Immunity:

Different Foes, Similar Battleground
Daolong Dou2 and Jian-Min Zhou1,*
1State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology,

Chinese Academy of Sciences, Beijing 100101, China

2College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China

*Correspondence: jmzhou@genetics.ac.cn
http://dx.doi.org/10.1016/j.chom.2012.09.003

Phytopathogenic bacteria, fungi, and oomycetes invade and colonize their host plants through distinct
routes. These pathogens secrete diverse groups of effector proteins that aid infection and establishment
of different parasitic lifestyles. Despite this diversity, a comparison of different plant-pathogen systems
has revealed remarkable similarities in the host immune pathways targeted by effectors from distinct path-
ogen groups. Immune signaling pathways mediated by pattern recognition receptors, phytohormone
homeostasis or signaling, defenses associated with host secretory pathways and pathogen penetrations,
and plant cell death represent some of the key processes controlling disease resistance against diverse path-
ogens. These immune pathways are targeted by effectors that carry a wide range of biochemical functions
and are secreted by completely different pathogen groups, suggesting that these pathways are a common
battleground encountered by many plant pathogens.

Introduction PRRs is referred to as pattern-triggered immunity (PTI; Tsuda

The rhizosphere and phyllosphere of terrestrial plants are home
to an enormous number of microorganisms, many of which are
potentially pathogenic at certain stages during their associations
with plants (Berendsen et al., 2012; Hirano and Upper, 2000).
These pathogens use diverse routes to penetrate physical
barriers and colonize host plants with different lifestyles.
However, plants are able to sense invading microbes, mount
effective defenses, and remain healthy the majority of time
(Jones and Dangl, 2006). Nonetheless, occasional breach of
the plant immune system by pathogens can cause severe
diseases to crop plants and poses a major threat to agriculture
(Cui et al., 2009; Oliva et al., 2010). The molecular bases of
plant disease resistance and microbial pathogenesis have
been the central questions for those studying plant-pathogen
interactions.
Like animals, plants possess a surveillance system detecting
conserved microbial molecular signatures, termed pathogen-
or microbe-associated molecular patterns (PAMPs), to trigger
immunity (Boller and Felix, 2009). In addition, host-derived
signals generated during pathogen infection or mechanical
damage, called damage-associated molecular patterns
(DAMPs), serve as another means by which the host senses
pathogen infection (D’Ovidio et al., 2004; Huffaker et al., 2006).
Receptors perceiving PAMPs and DAMPs are collectively called
pattern recognition receptors (PRRs). Unlike animal PRRs, which
consist of both plasma membrane-localized Toll-like receptors
(TLRs) and cytoplasmic NOD-like receptors (NLR), plant PRRs
are exclusively plasma membrane-localized receptor-like
kinases or receptor-like proteins (Monaghan and Zipfel, 2012).
Plants do carry a large number of NLR proteins, but they do
not appear to recognize PAMPs or DAMPs. Instead, plant
NLRs exclusively detect intracellular pathogen effector proteins
and trigger immune responses in a highly specific manner. In this
review, plant immunity triggered by PAMPs and DAMPs through
and Katagiri, 2010), whereas intracellular effector-triggered
immunity through NLRs is referred to as effector-triggered
immunity (ETI; Jones and Dangl, 2006). Together PTI and ETI
limit microbial entry, restrict pathogen propagation, or kill patho-
gens inside plant tissues.
Advances in microbial genomics have uncovered a large
number of effectors from phytopathogenic microbes devoted
to pathogenesis. Systematic characterization of effectors from
model pathogens such as the gram-negative bacteria Pseudo-
monas syringae and Xanthomonas spp. led to the identification
of multiple host targets, many of which are key players in the
plant immune system (Block and Alfano, 2011; Deslandes and
Rivas, 2012; Feng and Zhou, 2012). In contrast, relatively little
is known about host targets for effectors from filamentous path-
ogens, which include fungi and oomycetes. However, emerging
evidence suggests that several pathogenic strategies employed
by bacterial pathogens are also adopted by filamentous patho-
gens to subvert the host immune system (Bozkurt et al., 2012;
de Jonge et al., 2011; Oliva et al., 2010; Rafiqi et al., 2012).
Here we review plant immune mechanisms in the context of
different plant-pathogen systems and explore how effectors
from distinct pathogens have independently evolved to subvert
common host immune pathways.
Biology of Phytopathogens and Effectors
Based on their lifestyles on plants, phytopathogenic microbes
can be divided into biotrophs, hemibiotrophs, and necrotrophs.
While biotrophs feed on living cells and actively maintain host cell
viability, necrotrophs kill host cells before feeding on dead
tissues. Hemibiotroph adopts an early biotrophic phase followed
by a necrotrophic phase. Pathogen lifestyle is largely determined
by effectors, which are proteins and secondary metabolites
elaborated by the pathogen that directly interact with the host
and enhance virulence (Collmer et al., 2009; Hogenhout et al.,

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2009). This review primarily focuses on effectors of biotrophic
and hemibiotrophic pathogens that directly interfere with plant
immunity.
Hemibiotrophic bacterial pathogens such as Pseudomonads
and Xanthomonads enter plant tissues through natural openings
including stomata, hydathodes, and wounds (Figure 1A). Once
inside intercellular spaces or vascular tissues, the bacterium
senses the host environment and switches to a parasitic lifestyle
through extensive transcriptional reprogramming, although the
nature of the host signals that trigger this switch remains elusive
(Huynh et al., 1989; Lan et al., 2006; Tang et al., 2006).
Fungal and oomycete pathogens produce various types of
spores, which adhere to the plant surface. Upon stimulation by
appropriate signals, the spores germinate and form an extended
germ tube that migrates toward favorable infection sites on the
plant surface. The germ tube of most fungi and oomycetes
develops a specialized structure called appressorium, from
which a penetration peg directly pierces the cuticle and cell
wall layers through mechanical force and enzymatic softening
of the plant cell wall (Horbach et al., 2011). Inside host tissues,
the hyphal tip of some obligate biotrophs (e.g., Blumeria grami-
nis) or hemibiotrophs (e.g., Phytophthora infestans) projects
into the host cell through invagination of the host plasma
membrane, with the latter tightly surrounding the newly formed
pathogen membrane, forming a second specialized structure
called haustorium (Figures 1B and 1C; Horbach et al., 2011;
Kamoun, 2006). Haustoria are not only responsible for nutrient
Figure 1. Schematic Representation of
Infection Processes of Distinct Pathogen
Groups
(A) Invasion by bacterial pathogens through
stomata (e.g., P. syringae).
(B) Major events during hemibiotrophic fila-
mentous pathogen infection (e.g., Phytophthora
infestans). Note that plant cell death (orange)
occurs at the necrotrophic infection stage.
(C) Infection by obligated biotrophic pathogens
that form haustorium in the host cell (e.g., Blumeria
graminis).
(D) Infection by biotrophic pathogens that
only develop intercellular infection hyphae (e.g.,
C. fulvum). Pathogens are shown in purple,
whereas live plant cells are in green. Red and
yellow circles represent apoplastic and intracel-
lular effectors, respectively. Gc, germinated cysts;
Ap, appressorium; Spm, sporangium; Cm, conid-
ium; Gt, germ tube; Ih, infection hyphae; Sp,
spores; H, haustorium.
uptake but also represent the prime
site of effector secretion (Mendgen and
Hahn, 2002). In addition, some patho-
gens (e.g., Cladosporium fulvum and
Uromyces appendiculatus) enter plant
tissues through stomatal openings (Fig-
ure 1D; Thomma et al., 2005). The germ
tube of U. appendiculatus can accurately
locate the host stoma and form a tightly
fitted appressorium over it, from which
a fine hyphae grows into the plant tissue
(Hoch et al., 1987). C. fulvum invades
host cells by forming long, branched
intercellular hyphal structures with no obvious haustorium (Fig-
ure 1D; Thomma et al., 2005).
Phytopathogen effectors can be delivered into the apoplast,
the free space outside the plant plasma membrane, or inside
the host cell. Apoplastic effectors include cell wall-degrading
enzymes (CWDEs), toxins, and various cysteine-rich proteins.
CWDEs and toxins are important virulence factors for necrotr-
ophs but are thought to be less important for biotrophs and
hemibiotrophs (Barras et al., 1994; Cantu et al., 2008). Biotrophic
and hemibiotrophic fungal and oomycete pathogens secrete
a variety of cysteine-rich proteins into the host apoplast whose
stability is likely enhanced by intramolecular disulfide bridges
(Kamoun, 2006). Some of these effectors are inhibitors of host
antimicrobial hydrolytic enzymes including chitinases, gluca-
nases, and proteases (de Jonge et al., 2011; Oliva et al., 2010),
while others possess Lysine motifs (LysMs) capable of chitin
binding (Mentlak et al., 2012; Stergiopoulos and de Wit, 2009;
Thomma et al., 2005). These inhibitors not only serve to protect
the pathogen cell wall from destruction by host-derived lytic
enzymes, but also prevent the release of cell wall fragments
that are PAMPs detected by host PRRs (Figure 2). In addition,
some cysteine-rich effectors, such as necrosis and ethylene-
inducing peptide (NEP) family proteins, are found in diverse
pathogens, whereas the elicitin family is specific to oomycetes
(Kamoun, 2006). Apoplastic effectors can be recognized by plant
PRRs as PAMPs and trigger immune responses (Kamoun, 2006;
Qutob et al., 2006).
Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc. 485

Figure 2. Suppression of Plant PRR-Mediated Surveillance System
by Pathogen Effectors
Bacterial and filamentous pathogen-derived PAMPs, e.g., flg22 and chitin
fragments (Chi), induce host defense responses mediated by plant PRRs, e.g.,
FLS2, CEBiP, and CERK1. Intracellular effectors from P. syringae (AvrPto,
AvrPtoB, AvrPphB, HopF2, HopAI1, and HopU1), X. campestris campestris
(AvrAC), P. sojae (Avr3b and Avr1b), and H. arabidopsidis (ATR1 and ATR13)
target the indicated PTI signaling events inside the plant cell. Precise targets
for H. arabidopsidis ATR1 and ATR13 remain unknown. Apoplastic effectors
including C. fulvum Ecp6 and M. oryzae Slp1 compete with chitin receptors
CEBiP and CERK1 for chitin binding. The C. fulvum apoplastic effector Avr4
protects fungal hyphae from degradation by plant-derived chtinases (CHN).
Intracellular effectors are secreted mainly by biotrophic and
hemibiotrophic pathogens. Bacterial pathogens can deliver
these effectors into the host cell through the type III, type IV,
and type VI secretion systems. Among these, the type III secre-
tion system is of utmost importance for plant bacterial patho-
gens such as Pseudomonas syringae, Xanthomonas spp., and
Ralstonia solanacearum. The N terminus of type III effectors
displays biased amino acid composition and serves as a signal
recognized by the type III secretion machinery (Collmer et al.,
2002; Vinatzer et al., 2005). The type IV secretion system is
responsible for the delivery of Agrobacterial virulence proteins
and the transfer DNA into host cells (Christie, 2004).
Intracellular effectors of fungal and oomycete pathogens are
presumably targeted to extracellular spaces by their N-terminal
signal peptide before being translocated into the plant cell.
How these effectors are translocated into the plant cell is an
active area of investigation. Many oomycete effectors possess
a RXLR-dEER motif that serves as a signal for translocation
(Dou et al., 2008b; Whisson et al., 2007). A second class of
oomycete intracellular effectors, called CRN effectors, use
a FLAK motif for translocation (Schornack et al., 2010). It is likely
that other intracellular effectors also possess translocation
signals. For example, many candidate intracellular effectors
from cereal powdery mildew and rust pathogens possess a
Y/F/WxC motif that may serve as a novel signal for host cell entry
(Godfrey et al., 2010; Spanu et al., 2010). How these signals
assist in targeting effectors into the plant cell is not understood,
but the RXLR-dEER motif has been reported to mediate host cell
entry by binding to phosphatidyl inositol phosphates on the outer
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Cell Host & Microbe
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surface of plant plasma membranes (Kale et al., 2010), a finding
that is subject to some debate. It is not clear if intracellular
effectors of filamentous pathogens are translocated through a
specialized structure. Nonetheless, Magnaporthe oryzae intra-
cellular effectors have been found to preferentially accumulate
in the biotrophic interfacial complex (BIC), a novel interfacial
structure associated with the first invading hyphae (Khang
et al., 2010). Interestingly, several candidate effectors of Colleto-
trichum higginsianum are found to accumulate in the interfacial
bodies on the surface of biotrophic hyphae, reminiscent of BIC
(Kleemann et al., 2012). These exciting findings provide mecha-
nistic insights into effector translocation for these pathogens.
PRR-Mediated Surveillance System as a Major
Battleground
Our understanding of the PRR-mediated surveillance system
has increased exponentially in the past decade. Several PRRs,
such as FLS2 and EFR, which recognize bacterial flagellin and
EF-Tu, respectively, are leucine-rich repeat receptor kinases
that, upon binding to their ligands, recruit another receptor-like
kinase BAK1 or one of its close homologs to form an active
receptor complex (Chinchilla et al., 2007; Heese et al., 2007;
Schulze et al., 2010). However, at least some PRRs do not
require BAK1 for function. The chitin receptor kinase CERK1
(Miya et al., 2007; Wan et al., 2008) binds chitin through LysMs
in the ectodomain and apparently undergoes a ligand-induced
homodimerization to induce CERK1 phosphorylation and sig-
naling (Liu et al., 2012). In rice, chitin perception also requires a
receptor-like protein CEBiP, which contains two LysMs in the
ectodomain but lacks a cytoplasmic kinase domain (Kaku
et al., 2006). FLS2, EFR, and likely CERK1 constitutively interact
with the receptor-like cytoplasmic kinase (RLCK) BIK1 and its
close homolog PBL1 (Lu et al., 2010; Zhang et al., 2010). Activa-
tion of PRRs by PAMPs leads to BIK1 phosphorylation and its
subsequent dissociation from PRRs. While substrates of BIK1
remain to be identified, a number of downstream signaling
components have been identified for PTI signaling. Calcium
influx is triggered immediately following PAMP perception
(Jabs et al., 1997; Pugin et al., 1997; Ranf et al., 2011), and this
likely leads to the activation of several calcium-dependent
kinases (Boudsocq et al., 2010). In addition, rapid production
of reactive oxygen species (ROS) through the NADPH oxidase
RbohD (Zhang et al., 2007) and the PRX33 peroxidase (Daudi
et al., 2012), and activation of MAP kinase cascades (Nühse
et al., 2000) are also required for PTI defenses, which include
transcriptional activation of a number of defense-related genes,
biosynthesis and secretion of antimicrobial compounds, and
fortification of the plant cell wall. PRRs are also subject to posi-
tive and negative regulation through transcriptional control,
endocytosis, and ubiquitin-mediated degradation (Robatzek
et al., 2006; Boutrot et al., 2010; Mersmann et al., 2010, Lu
et al., 2011).
The importance of PTI in resistance against hemibiotrophic
bacteria is well established (Lacombe et al., 2010; Lee et al.,
2009; Zipfel et al., 2004). Emerging evidence indicates that PTI
is also critical for resistance against biotrophic, hemibiotrophic,
and necrotrophic fungi and oomycetes. For instance, BAK1
and its close homolog BKK1, which are coreceptors for
PRRs, are required for full resistance to Hyaloperonospora
Cell Host & Microbe
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arabidopsidis, an obligate oomycete pathogen specialized on
Arabidopsis (Roux et al., 2011). Similarly, BAK1 is also required
for Nicotiana benthamiana resistance to P. infestans, a hemibio-
trophic pathogen that caused the potato famine 1.5 centuries
ago (Chaparro-Garcia et al., 2011). Arabidopsis and tomato
plants lacking BIK1 are highly susceptible to the necrotrophic
pathogens B. cinerea and A. brassicicola (Abuqamar et al.,
2008; Veronese et al., 2006), suggesting that PTI is important
for resistance to necrotrophs. Indeed, pretreatment of Arabidop-
sis plants with PAMPs leads to increased resistance to B. cinerea
(Laluk et al., 2011). The importance of the BIK1 family of RLCKs
in plant immunity is gaining further support from the finding
that overexpression of a BIK1 family member in rice leads to in-
creased resistance to the rice pathogens X. oryzae and M. oryzae
(Dubouzet et al., 2011).
An intense search for P. syringae and X. campestris type III
effector targets has identified a number of targets operating in
PTI pathways (Figure 2; Block and Alfano, 2011; Deslandes and
Rivas, 2012; Feng and Zhou, 2012). Remarkably, at least four
type III effectors from P. syringae and X. campestris have been
found to target PRR complex components. The P. syringae
type III effector AvrPto directly targets FLS2 and EFR to block
PTI signaling (Xiang et al., 2008, 2011), likely through inhibiting
the PRR’s kinase activity (Xing et al., 2007). AvrPto may target
additional PRRs, as expression of AvrPto in plants leads to the
inhibition of defenses induced by multiple PAMPs. Another
P. syringae type III effector, AvrPtoB, also possesses kinase-inhi-
bition domains that can target BAK1, CERK1, and FLS2 (Cheng
et al., 2011; Gimenez-Ibanez et al., 2009; Göhre et al., 2008;
Zeng et al., 2011). These two effectors are of primary importance
for the well-studied P. syringae strain DC3000. Simultaneous
deletion of avrPto and avrPtoB from DC3000 not only causes
marked reduction of bacterial virulence but also renders other
type III effectors ineffective (Lin and Martin, 2005; Cunnac et al.,
2011). A third component of the PRR complex, BIK1, is targeted
by at least two type III effectors. The P. syringae effector AvrPphB,
a cysteine protease, can inhibit PTI signaling by cleaving multiple
members of the BIK1 family of RLCKs (Zhang et al., 2010). The
X. campestris effector AvrAC uses a novel uridylyl-transferase
activity to block the activation of BIK1, thereby promoting viru-
lence (Feng et al., 2012). Interestingly, the P. syringae type III
effector AvrB has been shown to interact with RIPK, another
BIK1 family, to modulate host defenses (Liu et al., 2011). Although
it is not known if this is related to the virulence function of AvrB,
this finding suggests that the BIK1 family of RLCKs is subject to
repeated attacks by many bacterial effectors.
While it remains to be seen if any filamentous pathogen effec-
tors directly attack PRR complex components, some fungal
pathogens have evolved alternative strategies to counter PRR
surveillance system in the host plant. LysM domain proteins
are widely distributed in fungal pathogens and have emerged
as important effectors (Bolton et al., 2008). The C. fulvum apo-
plastic effector Avr4 binds chitin through its LysMs and protects
the fungal cell wall from plant chitinases (van den Burg et al.,
2006). This may prevent the release of chitin and subsequent
detection of this PAMP by host chitin receptors (Figure 2). Impor-
tantly, the C. fulvum apoplastic effector ECP6 and the M. oryzae
apoplastic effector Slp1 have been shown to interfere with PRR
function (de Jonge et al., 2010; Mentlak et al., 2012). These effec-
tors possess three LysMs and compete with chitin receptors for
chitin binding, preventing fungal recognition in plants. Both
ECP6 and Slp1 are required for full virulence of the fungi,
indicating that avoiding host surveillance is important for the
establishment of parasitism. Thus bacterial and fungal patho-
gens have evolved different tactics to evade or block PRR-
mediated surveillance.
In addition to PRR complexes, pathogen effectors can target
downstream components to suppress PTI (Figure 2). The
P. syringae type III effectors, including HopAI1 and HopF2,
directly attack components of MAPK cascades to inhibit PTI
signaling (Wang et al., 2010; Zhang et al., 2007, 2010). HopAI1
is a phosphothreonine lyase that dephosphorylates MAP
kinases, whereas HopF2 uses ADP-ribosyltransferase activity
to inhibit MAP kinase kinases. In addition, P. syringae type III
effector HopU1 is a potent ADP ribosyl-transferase that specifi-
cally modifies RNA binding proteins GRP7 and GRP8, thereby
impeding their RNA-binding function and inhibiting plant immu-
nity (Fu et al., 2007; Jeong et al., 2011).
Although it remains to be seen if PTI signaling components are
similarly targeted by various filamentous pathogen effectors,
engineered delivery of a number of effectors including ATR1 and
ATR13 from the obligated oomycete pathogen H. arabidopsidis
through the P. syringae type III secretion system enhances
bacterial virulence (Fabro et al., 2011). This activity is correlated
with the ability of these effectors to inhibit PAMP-induced callose
deposition, suggesting that these effectors also target PTI
signaling pathway (Figure 2). The future identification and char-
acterization of host targets for these effectors are likely to bring
exciting insight into host immune mechanisms responsible for
resistance against a wide range of pathogens.
Phytohormone Signaling Is Targeted by Effectors
Plant hormone homeostasis and responses play a major role in
plant-pathogen interactions (Robert-Seilaniantz et al., 2011).
Salicylic acid (SA), ethylene (ET), and jasmonic acid (JA) are
dubbed defense hormones in plants. In many cases, SA is
required for resistance to biotrophic pathogens, whereas JA
and ET are required for resistance to necrotrophic pathogens.
The SA and JA/ET pathways act largely in an antagonistic
manner. Different plant hormones modulate plant immunity
and/or susceptibility through a complex hormone-hormone
interaction network and crosstalks with plant immune signaling
pathways (Robert-Seilaniantz et al., 2011). For example, treat-
ment of Arabidopsis with flg22, the bacterial flagellin-derived
elicitor peptide, induces the plant microRNA miR393, which
specifically represses transcripts of the auxin receptor gene
TIR1 (Navarro et al., 2006). Furthermore, activation of brassinos-
teroid signaling can both repress PTI signaling through a BAK1-
independent mechanism and enhance PTI signaling through
a BAK1-dependent mechanism (Albrecht et al., 2012; Belkhadir
et al., 2012). Thus accurate regulation of different hormonal
pathways is an inseparable part of the plant immune system.
Naturally, plant pathogens have evolved a variety of strategies
to overcome plant hormone-mediated immunity or induce host
susceptibility by interfering with various hormonal processes.
Many plant pathogens actively manipulate plant hormone
pathways for pathogenesis either through microbial production
of phytohormones or functional analogs of phytohormones or
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by activating hormonal signaling pathways. Accumulating
evidence indicates that pathogen effectors can modulate
hormonal responses in plants. For example, the P. syringae
type III effectors AvrB, AvrPtoB, and AvrRpt2 have been shown
to stimulate host gene expression that is normally induced by
JA, ABA, and auxin, respectively (He et al., 2004; Chen et al.,
2007; de Torres-Zabala et al., 2007). AvrPto and AvrPtoB induce
ET biosynthesis to stimulate cell death in tomato plants (Cohn
and Martin, 2005). The X. campestris pv. vesicatoria type III
effector AvrBs3 induces hypertrophy by transcriptionally acti-
vating auxin response gene expression (Kay et al., 2007).
Furthermore, effectors encoded by the P. syringae conserved
effector locus have been shown to suppress the SA-mediated
disease resistance (DebRoy et al., 2004).
How pathogen effectors alter plant hormone biosynthesis or
responses remains largely unknown. However, the P. syringae
type III effector HopI1 uses its J domain to interact with HSP70
in chloroplasts, and this interaction suppresses SA accumulation
through an unknown mechanism (Jelenska et al., 2007). Ustilago
maydis, a hemibiotrophic fungal pathogen, has evolved a
different strategy to inhibit SA biosynthesis in plants. Its intracel-
lular effector Cmu1 is a functional chorismate mutase that
converts chorismate to prephenate (Djamei et al., 2011). Choris-
mate is a key intermediate in the biosynthesis of SA (Wildermuth
et al., 2001), and the action of Cmu1 effectively depletes choris-
mate and suppresses SA accumulation. Interestingly, genes
encoding secreted chorismate mutases exist in many genomes
of eukaryotic biotrophic and hemibiotrophic plant pathogens
but occur rarely in necrotrophs, suggesting that this mechanism
is particularly important for biotrophs and hemibiotrophs (Djamei
et al., 2011). Collectively, these findings indicate that bacterial
and fungal pathogens have independently evolved different
intracellular effectors to actively suppress SA accumulation.
In plants, JA is perceived by receptor complexes consisting of
the COI1 F box protein and the JAZ family of transcription core-
pressors. Binding of JA to COI1 enables COI1-JAZ interaction
and subsequent ubiquitination and degradation of JAZ, enabling
JA response gene transcription (Chini et al., 2007; Thines et al.,
2007). AvrB perturbs JA signaling, as observed by the upregu-
lated expression of JA response genes. This effector has also
been shown to interact with MPK4, the RPM1-interacting protein
RIN4, and the HSP90 chaperone complex component RAR1.
AvrB induces MPK4 phosphorylation in a RAR1-dependent
manner, and this may lead to RIN4 phosphorylation. RAR1,
MPK4, and RIN4 are all required for AvrB-induced JA response
gene expression (Cui et al., 2010; Shang et al., 2006). It is not
known how the AvrB-MPK4-RIN4 pathway regulates JA sig-
naling, but COI1 is required, suggesting that AvrB may indirectly
regulate COI1- and JAZ-dependent signaling. It is interesting to
note that several H. arabidopsidis and P. syringae effectors have
been reported to interact with JAZ3 in a protein interactome
study, suggesting that these effectors can directly modulate
JA signaling (Mukhtar et al., 2011). Together these studies high-
light plant hormone-mediated immunity as another major battle-
ground for pathogen effectors.
Effectors Battling for Pathogen Entry
An understudied battleground is plant immune mechanisms that
restrict pathogen entry. Attempted penetration by filamentous
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pathogens is known to provoke plant defenses exemplified by
production of ROS, secretion of antimicrobial protein and
metabolites, and cell wall apposition. For example, infection of
Arabidopsis plants by the nonadapted powdery mildew path-
ogen Blumeria graminis f. sp. hordei (Bgh) triggers callose depo-
sition at the site of attempted penetration, and this response
correlates with the aborted penetration by this pathogen. Three
Arabidopsis genes, PEN1, PEN2, and PEN3, controlling this
penetration level resistance have been characterized (Collins
et al., 2003; Stein et al., 2006). PEN1, a plasma membrane-
resident syntaxin protein, forms a heterotrimeric SNARE
complex with SNAP33 and VAMP721/722 to control vesicle-
mediated exocytosis (Kwon et al., 2008). PEN2 is a myrosinase
that likely converts the pathogen-induced glucosinolates, which
are tryptophan-derived secondary metabolites, into products
with antimicrobial activity (Bednarek et al., 2009). PEN3, an
ATP-binding cassette transporter located in the plasma mem-
brane, is thought to play a role in the secretion of antimicrobial
products. How does a virulent powdery mildew fungus over-
come this penetration resistance? It has been postulated that
the adapted pathogen may have evolved tolerance to the antimi-
crobial compounds produced by the PEN2 pathway (Schulze-
Lefert and Panstruga, 2011). However, the adapted fungus
may also have evolved active mechanisms to suppress the
penetration resistance. Indeed, the adapted fungus does not
induce strong callose deposition at the site of penetration,
implying an active suppression or evasion of the host surveil-
lance system by this fungus.
A recent study on Colletotrichum higginsianum elegantly
showed that some of the effectors expressed early during the
infection are secreted through the appressorial penetration
pore before the penetration peg is called into action (Kleemann
et al., 2012). An intriguing possibility is that these effectors act
as ‘‘anesthetic agents’’ that calm the host cell, so that the subse-
quent penetration is met with minimal resistance. Another recent
study on the U. maydis apoplastic effector Pep1 provides
exciting insights into the mechanism by which this fungal path-
ogen overcomes penetration resistance in plants (Figure 3).
A U. maydis strain lacking the Pep1 gene elicits strong penetra-
tion resistance exemplified by the accumulation of hydrogen
peroxide and callose at the site of penetration (Hemetsberger
et al., 2012). In contrast, these responses were largely sup-
pressed by the wild-type fungus, indicating that Pep1 plays
a crucial role in the suppression of this penetration resistance.
Further analysis showed that Pep1 directly targeted the maize
apoplastic peroxidase POX12, and U. maydis penetration was
inhibited by application of horse radish peroxidase, which
belongs to the same family of peroxidase as POX12. Conversely,
silencing of POX12 suppressed ROS production and allowed the
penetration by the Pep1-deletion mutant strain. These results
indicate that, like the PRX33 peroxidase which is involved in
ROS production during PTI (Daudi et al., 2012), POX12 is
required for ROS production, and that specific targeting of
POX12 by Pep1 suppresses the penetration resistance mediated
by ROS (Hemetsberger et al., 2012).
Penetration immunity also plays a key role in bacterial resis-
tance in plants. The initial exposure of plants to P. syringae
rapidly induces stomatal closure upon the perception of PAMPs
by the immune receptor FLS2, significantly reducing bacterial
Cell Host & Microbe
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Figure 3. Effectors Interfering with Penetration Immunity
The U. maydis apoplastic effector Pep1 binds to and inhibits a host peroxidase
(POX12) in the apoplast to suppress the production of reactive oxygen species
(e.g., H2O2) and papillae (orange) formation at the penetration site. P. syringae
produces coronatine (COR) to promote stomatal opening. P. syringae type III
effectors AvrB, AvrPto, and AvrPtoB may interfere with stomatal closure via
different mechanisms, although their translocation into the guard cell remains
to be shown. GC, guard cell.
entry (Melotto et al., 2006; Zeng and He, 2010). The canonical
abscisic acid (ABA) signaling pathway is required for the FLS2-
triggered stomatal closure, illustrating how the PRR surveillance
system co-opts an existing abiotic stress response pathway for
defenses. Interestingly, hydrogen peroxide plays an important
role in stomata penetration resistance, as the ABA-induced
production of H2O2 is known to trigger stomatal closure through
a receptor-like kinase, GHR1 (Hua et al., 2012). Furthermore,
a recent study showed that an aspartate oxidase is required
for elf18-induced H2O2 production and stomatal closure (Macho
et al., 2012), further supporting the importance of H2O2 in PAMP-
induced penetration resistance.
Strikingly, some virulent P. syringae bacteria produce a toxin
called coronatine which structurally and functionally mimics JA-
Ile, an active form of JA. These bacteria are capable of reversing
the PAMP-induced stomatal closure through crosstalk between
JA and ABA signaling pathways (Figure 3; Melotto et al., 2006). It
is not known if any effector proteins modulate stomatal opening.
However, it was recently shown that RIN4 positively regulates
plasma membrane proton ATPases AHA1 and AHA2 to open
stomata (Liu et al., 2009). The fact that RIN4 is a target of
AvrB raises the possibility that AvrB may enhance virulence by
promoting stomatal opening, although it is not known if AvrB
is delivered into the guard cell. Since AvrB is known to regulate
RIN4 phosphorylation through MPK4 and RIPK, it is tempting to
speculate that these phosphorylations may play a role in regu-
lating the proton ATPases that regulate stomatal aperture.
Furthermore, the ability of AvrPto and AvrPtoB to block PRR
signaling may also suppress stomata penetration resistance
(Figure 3). P. syringae mutants in which the avrPto and avrPtoB
genes are deleted show virulence defects specifically when
Arabidopsis plants are challenged through leaf surface, but
not when they are infiltrated into leaves (He et al., 2006; Xiang
et al., 2008). Type III effector genes are expressed largely after
penetration, raising the question of whether the bacterium is
able to inject type III effectors into the guard cell prior to pene-
tration. However, at least some type III effectors have been
shown to be expressed during epiphytic association (Lee
et al., 2012). Alternatively, a small number of bacteria that
have entered into the substomatal chamber before PAMP-
induced stomatal closure may allow the injection of type III
effectors into the guard cell. It is interesting to note that AvrB
can at least partially complement the coronatine deficiency of
a P. syringae strain (He et al., 2004), further raising the possibility
that AvrB can phenocopy coronatine to regulate stomatal
opening (Figure 3).
Effectors Targeting Secretory Pathway-Associated
Immunity
Rapid and polarized delivery of vesicles containing various anti-
microbial metabolites and proteins into the apoplast, where the
pathogen resides, is critical to halt pathogen infection (Frei dit
Frey and Robatzek, 2009; Hückelhoven, 2007). The trans-Golgi
network/early endosome (TGN/EE) is likely responsible for the
production of these vesicles during defenses. Indeed, it was
recently shown that the Arabidopsis protein MIN7, an ADP ribo-
sylation factor guanine nucleotide exchange factor associated
with TGN/EE, is required not only for PTI, but also for ETI and
SA-induced resistance to P. syringae (Nomura et al., 2011).
The PEN1-SNAP-VAMP721/722 SNARE complex likely controls
the deposition of antimicrobial cargo, as VAMP722 is associated
with vesicles and mobilizes to the site of attempted penetration
(Kwon et al., 2008).
The first piece of evidence that plant pathogens actively
manipulate the immune secretory pathway came from the study
of the P. syringae type III effector HopM1, which directly inter-
acts with MIN7 (Nomura et al., 2006). HopM1 induces MIN7
degradation in a proteasome-dependent manner, but the bio-
chemical function of HopM1 remains unknown. While it remains
to be explored if any filamentous pathogen effectors directly
interfere with host secretory pathway, the P. infestans protein
AVRblb2, an RXLR effector, has been shown to block the secre-
tion of the host papain-like cysteine protease (PLCP) C14
(Bozkurt et al., 2011). Transient overexpression of AVRblb2 in
plants significantly enhances susceptibility, whereas overex-
pression of C14 enhances host resistance to P. infestans. The
mechanism by which AVRblb2 inhibits C14 secretion is not
known. However, the Arabidopsis apoplastic PLCP RD19 can
be redirected to the nucleus by the R. solanacearum type III
effector PopP2 when the latter is expressed as a transgene
(Bernoux et al., 2008), suggesting that this bacterial pathogen
has evolved a unique strategy to prevent PLCP secretion. Extra-
cellular PLCPs are additionally targeted by apoplastic effectors
from both oomycete and fungal pathogens. P. infestans ex-
tracellular protease inhibitors (EPICs) EPIC1 and EPIC2B
have been shown to bind and inhibit tomato apoplastic PLCPs
RCR3 and PIP1 with overlapping specificities (Song et al.,
2009). Similarly, the C. fulvum apoplast effector Avr2 also
possesses EPIC activity and targets RCR3 and PIP1 (Song
et al., 2009). These findings suggest that secretion of extracel-
lular PLCPs is of critical importance to plant immunity and
that pathogens have evolved both intracellular effectors and
apoplastic effectors to counter this immunity.
Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc. 489

Effectors Manipulating Plant Cell Death
A major consequence of pathogen infection is plant cell death. In
plant-biotrophic pathogen interactions, recognition of the path-
ogen by NLRs and PRRs often leads to the hypersensitive
response (HR; Coll et al., 2011), a programmed cell death that
is thought to restrict the pathogen to a small number of infected
host cells, although disease resistance and the HR can be un-
coupled in some cases. Thus successful biotrophs must actively
suppress HR. In contrast, active killing of host cells is promoted
by the pathogen to facilitate the infection in plant-necrotroph
interactions (Mengiste, 2012). In plant-hemibiotrophs interac-
tions, host cell death is likely suppressed by the pathogen in
the biotrophic phase but promoted during necrotrophic phase
(Coll et al., 2011). This differential manipulation of host cell death
is likely to be critical for the phase transition of these pathogens.
Because some effectors are recognized by NLRs and PRRs in
the host plant, it is common that biotrophs and hemibiotrophs
accumulate mutations in these effector genes to evade recogni-
tion and avoid the triggering of HR. These pathogens also deploy
effectors to actively suppress HR. Nearly half of the annotated
Phytophthora RXLR effectors and a quarter of H. arabidopsidis
RXLR effectors contain a WY domain, which forms a conserved
a-helical protein fold (Bozkurt et al., 2012). Functional analysis of
the P. sojae effector Avr1b indicates that the WY domain is
required for cell death inhibition (Dou et al., 2008a). Interestingly,
this domain is not found in necrotrophic oomycete pathogen
Pythium ultimum RXLR effectors (Bozkurt et al., 2012), sug-
gesting that biotrophic (H. arabidopsidis) or hemibiotrophic
oomycete (Phytophthora) pathogens have devoted a large
number of RXLR effectors to the biotrophic lifestyle by suppress-
ing host cell death. Inhibition of HR may also represent a major
function for bacterial pathogenesis, as most of the P. syringae
type III effectors are able to suppress the ETI-associated HR
(Guo et al., 2009).
A number of effectors have been shown to inhibit HR by
attacking the host surveillance system. The P. infestans RXLR
effector IPI-O1 has been reported to target the legume-like
lectin receptor kinase LecRK-1.9 in the apoplast to destabilize
continuum of the host cell wall and plasma membrane (Bouw-
meester et al., 2011). A recent report, however, showed that it
also triggers HR through a direct interaction with the coiled-
coil (CC) domain of the potato NLR protein RB (Chen et al.,
2012). This finding implies a cytoplasmic localization of IPI-O1.
Interestingly, another RXLR effector IPI-O4 is able to inhibit this
HR by interacting with the same RB CC domain. The RB activa-
tion is likely mediated by the oligomerization of the CC domain,
and IPI-O4 may interfere with this oligomerization or block inter-
actions of the CC domain with other signaling components.
Effectors can also inhibit the HR by interfering with host proteins
required for NLR function. For example, AvrB induces RIN4T166
phosphorylation through RIPK (Liu et al., 2011), and this phos-
phorylation results in the activation of the NLR protein RPM1
(Chung et al., 2011; Liu et al., 2011). At least two type III effectors
are known to interfere with the RPM1-specified HR. AvrAC does
so by uridylylating RIPK (Feng et al., 2012), whereas AvrRpt2,
a cysteine protease, blocks this HR by specifically degrading
RIN4 (Kim et al., 2005). Some Arabidopsis plants carry another
NLR protein RPS2 to recognize AvrRpt2 and trigger HR. RPS2
is kept at an off state through a physical interaction with RIN4
490 Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc.
Cell Host & Microbe
Review
but activated upon the cleavage of RIN4 by AvrRpt2. It was
recently shown that HopF2 can directly interact with RIN4 to
block the RIN4 cleavage by AvrRpt2, thereby blocking the
RPS2-specific HR (Wilton et al., 2010). Pathogen effectors can
also act downstream of immune receptors to block cell death.
The P. infestans RXLR effector Avr3a has been shown to
suppress HR by interacting with and stabilizing CMPG1, a host
E3 ubiquitin ligase that negatively regulates HR controlled by
multiple PRRs and NLRs (Bos et al., 2010). The P. sojae RXLR
effector Avr3b contains a Nudix hydrolase motif to mimic host
ADP-ribose/NADH pyrophosphorylase and represses plant
defenses. This motif is essential for the inhibition of ROS accu-
mulation in Nicotiana benthamiana and suppression of the HR
in soybean (Dong et al., 2011). Furthermore, the inhibition of
the maize peroxidase POX12 by U. maydis Pep1 enables the
fungus to suppress the ROS-induced cell death (Hemetsberger
et al., 2012).
The necrotrophic phase is an integral part of hemibiotroph
pathogenesis. Emerging evidence indicates that hemibiotrophic
pathogens have evolved secondary metabolites (Howlett, 2006)
and effectors to actively promote host cell death. For example,
NEP-like proteins (NLPs) that are broadly distributed from
prokaryotic to eukaryotic pathogens are known to induce cell
death in dicotyledonous plants (Qutob et al., 2006). Overexpres-
sion of NLPs in C. coccodes not only dramatically increases its
aggressiveness on the host plant but also expands its host range
(Amsellem et al., 2002). Deletion of the gene in Pectobacterium
carotovorum reduces its aggressiveness on potato tubers
(Ottmann et al., 2009). These results suggest that NLPs benefit
necrotrophic growth of these pathogens by promoting host cell
death, at least in dicots. It is not known, however, if any NLPs
from obligate biotrophs and monocot plant pathogens con-
tribute to aggressiveness. In addition to NLPs, several P. sojae
RXLR effectors expressed in the necrotrophic phase are also
known to trigger host cell death (Wang et al., 2011). Genetic
evidence is needed to establish whether these RXLR effectors
enhance pathogen aggressiveness by promoting host cell death.
It is not clear how the effectors mentioned above trigger host
cell death. NLPs can induce comprehensive immune responses
resembling that evoked by bacterial flagellin, suggesting an
involvement of PRRs (Qutob et al., 2006). The NLP-induced
cell death in dicotyledonous plants is light dependent and at
least partially requires HSP90 (Qutob et al., 2006), which is
known to be required for NLR-induced HR. In a separate study,
a NLP from the necrotrophic pathogen Pythium aphanidermatum
was shown to exhibit structural similarities to actinoporins,
a group of cytolytic toxins that form transmembrane pores to
cause membrane disintegration (Ottmann et al., 2009). It remains
to be determined if the cell death induced by this NLP involves
active participation of the host plant. It is worth noting that the
necrotrophic pathogen Cochliobolus victoriae, which produces
a host-killing toxin called victorin, requires the Arabidopsis
NLR protein LOV1 for victorin sensitivity and virulence (Lorang
et al., 2007). These findings indicate that the programmed cell
death normally involved in plant immunity can be exploited by
phytopathogens for necrotrophy.
Hemibiotrophic bacterial pathogens may also actively induce
cell death for pathogenesis. For instance, it was reported that
HopM1 is required for P. syringae to cause disease lesions on
Cell Host & Microbe
Review
tomato plants (Badel et al., 2003). AvrPto and AvrPtoB have been
shown to promote cell death and disease lesion development on
tomato plants in an ET-dependent manner at late stages of
disease (Cohn and Martin, 2005). Likewise, the X. campestris
type III effector XopN is required to promote tomato leaf necrosis
at late stages of disease (Kim et al., 2009). XopN interacts with
TARK1, a receptor-like kinase, and TFT1, a 14-3-3 protein.
Genetic evidence indicated that TARK1 and the XopN-TFT1
interaction are required for the XopN-induced necrosis (Kim
et al., 2009; Taylor et al., 2012). It should be pointed out that
these bacterial effectors also contribute to virulence at early
stages of disease before necrosis develops, suggesting that
they play a dual role in virulence.
Delicate control of biotrophic and necrotrophic phases is crit-
ical for hemibiotrophs. This likely involves the timely expression
of effectors with opposing activities of host cell death manipula-
tion (Wang et al., 2011). Intracellular effectors that suppress host
cell death are often expressed during the biotrophic phase,
whereas NLPs and some of the death-inducing RXLR effector
genes are expressed in the necrotrophic phase. For example,
NLPs in P. sojae and C. higginsianum are highly induced during
the transition from biotrophy to necrotrophy (Kleemann et al.,
2012). In contrast, the P. infestans effector gene SNE1, which
inhibits NLP-induced cell death when transiently expressed in
plants, is highly expressed in the biotrophic phase but decreases
concomitantly with the increased expression of NLPs (Kelley
et al., 2010). Similarly, some of the C. higginsianum effectors ex-
pressed during the biotrophic phase can inhibit cell death when
artificially expressed in plants and promote bacterial infection
when delivered by P. syringae (Kleemann et al., 2012), whereas
most lytic enzymes are induced at the switch to necrotrophy
(O’Connell et al., 2012). Future genetic studies are needed to
establish if the death control by these effectors is responsible
for proper phase transition and pathogenesis in these hemibio-
trophs.
Conclusions
Bacterial, fungal, and oomycete pathogens secrete distinct
classes of effectors into the apoplast or inside the plant cell.
Our understanding of how these effectors promote parasitism
has largely derived from studies on bacterial type III effectors.
However, emerging data suggest that several key processes in
plant immunity are targeted by effectors from not only bacterial
pathogens, but also fungal and oomycete pathogens. Subver-
sion of host immunity can be achieved via apoplastic effectors
and intracellular effectors possessing completely unrelated
biochemical functions, illustrating how different microbes have
independently evolved mechanisms to inhibit common immune
pathways in plants. Recent advances in microbial genomics
have identified numerous effectors from various phytopatho-
gens, particularly filamentous pathogens. Characterization of
these effectors provides tremendous opportunity to probe the
aforementioned immune pathways.
ACKNOWLEDGMENTS
The authors would like to thank Wenbo Ma for comments on the manuscript,
Meng Li for assistance with the literature, and Danyu Shen for drawing
the diagrams. J.-M.Z. was supported by grants from the Chinese Ministry
of Science and Technology (2011CB100700; 2010CB835301). D.D. was
supported by grants from the National Natural Science Foundation of China
(number 30971830) and Natural Science Foundation of Jiangsu Province
(number BK2012027).
REFERENCES
Abuqamar, S., Chai, M.F., Luo, H., Song, F., and Mengiste, T. (2008). Tomato
protein kinase 1b mediates signaling of plant responses to necrotrophic fungi
and insect herbivory. Plant Cell 20, 1964–1983.
Albrecht, C., Boutrot, F., Segonzac, C., Schwessinger, B., Gimenez-Ibanez,
S., Chinchilla, D., Rathjen, J.P., de Vries, S.C., and Zipfel, C. (2012). Brassinos-
teroids inhibit pathogen-associated molecular pattern-triggered immune
signaling independent of the receptor kinase BAK1. Proc. Natl. Acad. Sci.
USA 109, 303–308.
Amsellem, Z., Cohen, B.A., and Gressel, J. (2002). Engineering hypervirulence
in a mycoherbicidal fungus for efficient weed control. Nat. Biotechnol. 20,
1035–1039.
Badel, J.L., Nomura, K., Bandyopadhyay, S., Shimizu, R., Collmer, A., and He,
S.Y. (2003). Pseudomonas syringae pv. tomato DC3000 HopPtoM (CEL ORF3)
is important for lesion formation but not growth in tomato and is secreted and
translocated by the Hrp type III secretion system in a chaperone-dependent
manner. Mol. Microbiol. 49, 1239–1251.
Barras, F., Gijsegem, F.v., and Chatterjee, A.K. (1994). Extracellular enzymes
and pathogenesis of soft-rot Erwinia. Annu. Rev. Phytopathol. 32, 201–234.
Bednarek, P., Pislewska-Bednarek, M., Svatos, A., Schneider, B., Doubsky, J.,
Mansurova, M., Humphry, M., Consonni, C., Panstruga, R., Sanchez-Vallet, A.,
et al. (2009). A glucosinolate metabolism pathway in living plant cells mediates
broad-spectrum antifungal defense. Science 323, 101–106.
Belkhadir, Y., Jaillais, Y., Epple, P., Balsemão-Pires, E., Dangl, J.L., and Chory,
J. (2012). Brassinosteroids modulate the efficiency of plant immune responses
to microbe-associated molecular patterns. Proc. Natl. Acad. Sci. USA 109,
297–302.
Berendsen, R.L., Pieterse, C.M., and Bakker, P.A. (2012). The rhizosphere
microbiome and plant health. Trends Plant Sci. 17, 478–486.
Bernoux, M., Timmers, T., Jauneau, A., Brière, C., de Wit, P.J., Marco, Y., and
Deslandes, L. (2008). RD19, an Arabidopsis cysteine protease required for
RRS1-R-mediated resistance, is relocalized to the nucleus by the Ralstonia
solanacearum PopP2 effector. Plant Cell 20, 2252–2264.
Block, A., and Alfano, J.R. (2011). Plant targets for Pseudomonas syringae type
III effectors: virulence targets or guarded decoys? Curr. Opin. Microbiol. 14,
39–46.
Boller, T., and Felix, G. (2009). A renaissance of elicitors: perception of
microbe-associated molecular patterns and danger signals by pattern-
recognition receptors. Annu. Rev. Plant Biol. 60, 379–406.
Bolton, M.D., van Esse, H.P., Vossen, J.H., de Jonge, R., Stergiopoulos, I.,
Stulemeijer, I.J., van den Berg, G.C., Borrás-Hidalgo, O., Dekker, H.L., de Kos-
ter, C.G., et al. (2008). The novel Cladosporium fulvum lysin motif effector Ecp6
is a virulence factor with orthologues in other fungal species. Mol. Microbiol.
69, 119–136.
Bos, J.I., Armstrong, M.R., Gilroy, E.M., Boevink, P.C., Hein, I., Taylor, R.M.,
Zhendong, T., Engelhardt, S., Vetukuri, R.R., Harrower, B., et al. (2010).
Phytophthora infestans effector AVR3a is essential for virulence and manipu-
lates plant immunity by stabilizing host E3 ligase CMPG1. Proc. Natl. Acad.
Sci. USA 107, 9909–9914.
Boudsocq, M., Willmann, M.R., McCormack, M., Lee, H., Shan, L., He, P.,
Bush, J., Cheng, S.H., and Sheen, J. (2010). Differential innate immune signal-
ling via Ca(2+) sensor protein kinases. Nature 464, 418–422.
Boutrot, F., Segonzac, C., Chang, K.N., Qiao, H., Ecker, J.R., Zipfel, C., and
Rathjen, J.P. (2010). Direct transcriptional control of the Arabidopsis immune
receptor FLS2 by the ethylene-dependent transcription factors EIN3 and
EIL1. Proc. Natl. Acad. Sci. USA 107, 14502–14507.
Bouwmeester, K., de Sain, M., Weide, R., Gouget, A., Klamer, S., Canut, H.,
and Govers, F. (2011). The lectin receptor kinase LecRK-I.9 is a novel
Phytophthora resistance component and a potential host target for a RXLR
effector. PLoS Pathog. 7, e1001327. http://dx.doi.org/10.1371/journal.ppat.
1001327.
Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc. 491

Bozkurt, T.O., Schornack, S., Win, J., Shindo, T., Ilyas, M., Oliva, R., Cano,
L.M., Jones, A.M., Huitema, E., van der Hoorn, R.A., and Kamoun, S. (2011).
Phytophthora infestans effector AVRblb2 prevents secretion of a plant immune
protease at the haustorial interface. Proc. Natl. Acad. Sci. USA 108, 20832–
20837.
Bozkurt, T.O., Schornack, S., Banfield, M.J., and Kamoun, S. (2012).
Oomycetes, effectors, and all that jazz. Curr. Opin. Plant Biol. 15, 483–492.
Cantu, D., Vicente, A.R., Labavitch, J.M., Bennett, A.B., and Powell, A.L.
(2008). Strangers in the matrix: plant cell walls and pathogen susceptibility.
Trends Plant Sci. 13, 610–617.
Chaparro-Garcia, A., Wilkinson, R.C., Gimenez-Ibanez, S., Findlay, K., Coffey,
M.D., Zipfel, C., Rathjen, J.P., Kamoun, S., and Schornack, S. (2011). The
receptor-like kinase SERK3/BAK1 is required for basal resistance against
the late blight pathogen phytophthora infestans in Nicotiana benthamiana.
PLoS ONE 6, e16608. http://dx.doi.org/10.1371/journal.pone.0016608.
Chen, Z., Agnew, J.L., Cohen, J.D., He, P., Shan, L., Sheen, J., and Kunkel,
B.N. (2007). Pseudomonas syringae type III effector AvrRpt2 alters Arabidopsis
thaliana auxin physiology. Proc. Natl. Acad. Sci. USA 104, 20131–20136.
Chen, Y., Liu, Z., and Halterman, D.A. (2012). Molecular determinants of
resistance activation and suppression by Phytophthora infestans effector
IPI-O. PLoS Pathog. 8, e1002595. http://dx.doi.org/10.1371/journal.ppat.
1002595.
Cheng, W., Munkvold, K.R., Gao, H., Mathieu, J., Schwizer, S., Wang, S., Yan,
Y.B., Wang, J., Martin, G.B., and Chai, J. (2011). Structural analysis of
Pseudomonas syringae AvrPtoB bound to host BAK1 reveals two similar
kinase-interacting domains in a type III Effector. Cell Host Microbe 10,
616–626.
Chinchilla, D., Zipfel, C., Robatzek, S., Kemmerling, B., Nürnberger, T., Jones,
J.D., Felix, G., and Boller, T. (2007). A flagellin-induced complex of the receptor
FLS2 and BAK1 initiates plant defence. Nature 448, 497–500.
Chini, A., Fonseca, S., Fernández, G., Adie, B., Chico, J.M., Lorenzo, O.,
Garcı́a-Casado, G., López-Vidriero, I., Lozano, F.M., Ponce, M.R., et al.
(2007). The JAZ family of repressors is the missing link in jasmonate signalling.
Nature 448, 666–671.
Christie, P.J. (2004). Type IV secretion: the Agrobacterium VirB/D4 and related
conjugation systems. Biochim. Biophys. Acta 1694, 219–234.
Chung, E.H., da Cunha, L., Wu, A.J., Gao, Z., Cherkis, K., Afzal, A.J., Mackey,
D., and Dangl, J.L. (2011). Specific threonine phosphorylation of a host target
by two unrelated type III effectors activates a host innate immune receptor in
plants. Cell Host Microbe 9, 125–136.
Cohn, J.R., and Martin, G.B. (2005). Pseudomonas syringae pv. tomato type III
effectors AvrPto and AvrPtoB promote ethylene-dependent cell death in
tomato. Plant J. 44, 139–154.
Coll, N.S., Epple, P., and Dangl, J.L. (2011). Programmed cell death in the plant
immune system. Cell Death Differ. 18, 1247–1256.
Collins, N.C., Thordal-Christensen, H., Lipka, V., Bau, S., Kombrink, E., Qiu,
J.L., Hückelhoven, R., Stein, M., Freialdenhoven, A., Somerville, S.C., and
Schulze-Lefert, P. (2003). SNARE-protein-mediated disease resistance at
the plant cell wall. Nature 425, 973–977.
Collmer, A., Lindeberg, M., Petnicki-Ocwieja, T., Schneider, D.J., and Alfano,
J.R. (2002). Genomic mining type III secretion system effectors in Pseudo-
monas syringae yields new picks for all TTSS prospectors. Trends Microbiol.
10, 462–469.
Collmer, A., Schneider, D.J., and Lindeberg, M. (2009). Lifestyles of the
effector rich: genome-enabled characterization of bacterial plant pathogens.
Plant Physiol. 150, 1623–1630.
Cui, H., Xiang, T., and Zhou, J.M. (2009). Plant immunity: a lesson from path-
ogenic bacterial effector proteins. Cell. Microbiol. 11, 1453–1461.
Cui, H., Wang, Y., Xue, L., Chu, J., Yan, C., Fu, J., Chen, M., Innes, R.W., and
Zhou, J.M. (2010). Pseudomonas syringae effector protein AvrB perturbs
Arabidopsis hormone signaling by activating MAP kinase 4. Cell Host Microbe
7, 164–175.
Cunnac, S., Chakravarthy, S., Kvitko, B.H., Russell, A.B., Martin, G.B., and
Collmer, A. (2011). Genetic disassembly and combinatorial reassembly
492 Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc.
Cell Host & Microbe
Review
identify a minimal functional repertoire of type III effectors in Pseudomonas
syringae. Proc. Natl. Acad. Sci. USA 108, 2975–2980.
Daudi, A., Cheng, Z., O’Brien, J.A., Mammarella, N., Khan, S., Ausubel, F.M.,
and Bolwell, G.P. (2012). The apoplastic oxidative burst peroxidase in Arabi-
dopsis is a major component of pattern-triggered immunity. Plant Cell 24,
275–287.
DebRoy, S., Thilmony, R., Kwack, Y.B., Nomura, K., and He, S.Y. (2004). A
family of conserved bacterial effectors inhibits salicylic acid-mediated basal
immunity and promotes disease necrosis in plants. Proc. Natl. Acad. Sci.
USA 101, 9927–9932.
de Jonge, R., van Esse, H.P., Kombrink, A., Shinya, T., Desaki, Y., Bours, R.,
van der Krol, S., Shibuya, N., Joosten, M.H., and Thomma, B.P. (2010).
Conserved fungal LysM effector Ecp6 prevents chitin-triggered immunity in
plants. Science 329, 953–955.
de Jonge, R., Bolton, M.D., and Thomma, B.P. (2011). How filamentous
pathogens co-opt plants: the ins and outs of fungal effectors. Curr. Opin. Plant
Biol. 14, 400–406.
Deslandes, L., and Rivas, S. (2012). Catch me if you can: bacterial effectors
and plant targets. Trends Plant Sci. Published online July 13, 2012. http://
dx.doi.org/10.1016/j.tplants.2012.06.011.
de Torres-Zabala, M., Truman, W., Bennett, M.H., Lafforgue, G., Mansfield,
J.W., Rodriguez Egea, P., Bögre, L., and Grant, M. (2007). Pseudomonas
syringae pv. tomato hijacks the Arabidopsis abscisic acid signalling pathway
to cause disease. EMBO J. 26, 1434–1443.
Djamei, A., Schipper, K., Rabe, F., Ghosh, A., Vincon, V., Kahnt, J., Osorio, S.,
Tohge, T., Fernie, A.R., Feussner, I., et al. (2011). Metabolic priming by
a secreted fungal effector. Nature 478, 395–398.
Dong, S., Yin, W., Kong, G., Yang, X., Qutob, D., Chen, Q., Kale, S.D., Sui, Y.,
Zhang, Z., Dou, D., et al. (2011). Phytophthora sojae avirulence effector Avr3b
is a secreted NADH and ADP-ribose pyrophosphorylase that modulates plant
immunity. PLoS Pathog. 7, e1002353. http://dx.doi.org/10.1371/journal.ppat.
1002353.
Dou, D., Kale, S.D., Wang, X., Chen, Y., Wang, Q., Wang, X., Jiang, R.H.,
Arredondo, F.D., Anderson, R.G., Thakur, P.B., et al. (2008a). Conserved
C-terminal motifs required for avirulence and suppression of cell death by
Phytophthora sojae effector Avr1b. Plant Cell 20, 1118–1133.
Dou, D., Kale, S.D., Wang, X., Jiang, R.H., Bruce, N.A., Arredondo, F.D.,
Zhang, X., and Tyler, B.M. (2008b). RXLR-mediated entry of Phytophthora
sojae effector Avr1b into soybean cells does not require pathogen-encoded
machinery. Plant Cell 20, 1930–1947.
D’Ovidio, R., Mattei, B., Roberti, S., and Bellincampi, D. (2004). Polygalactur-
onases, polygalacturonase-inhibiting proteins and pectic oligomers in plant-
pathogen interactions. Biochim. Biophys. Acta 1696, 237–244.
Dubouzet, J.G., Maeda, S., Sugano, S., Ohtake, M., Hayashi, N., Ichikawa, T.,
Kondou, Y., Kuroda, H., Horii, Y., Matsui, M., et al. (2011). Screening for resis-
tance against Pseudomonas syringae in rice-FOX Arabidopsis lines identified
a putative receptor-like cytoplasmic kinase gene that confers resistance to
major bacterial and fungal pathogens in Arabidopsis and rice. Plant Bio-
technol. J. 9, 466–485.
Fabro, G., Steinbrenner, J., Coates, M., Ishaque, N., Baxter, L., Studholme,
D.J., Körner, E., Allen, R.L., Piquerez, S.J., Rougon-Cardoso, A., et al.
(2011). Multiple candidate effectors from the oomycete pathogen Hyalopero-
nospora arabidopsidis suppress host plant immunity. PLoS Pathog. 7,
e1002348. http://dx.doi.org/10.1371/journal.ppat.1002348.
Feng, F., and Zhou, J.M. (2012). Plant-bacterial pathogen interactions medi-
ated by type III effectors. Curr. Opin. Plant Biol. 15, 469–476.
Feng, F., Yang, F., Rong, W., Wu, X., Zhang, J., Chen, S., He, C., and Zhou,
J.M. (2012). A Xanthomonas uridine 50 -monophosphate transferase inhibits
plant immune kinases. Nature 485, 114–118.
Frei dit Frey, N., and Robatzek, S. (2009). Trafficking vesicles: pro or contra
pathogens? Curr. Opin. Plant Biol. 12, 437–443.
Fu, Z.Q., Guo, M., Jeong, B.R., Tian, F., Elthon, T.E., Cerny, R.L., Staiger, D.,
and Alfano, J.R. (2007). A type III effector ADP-ribosylates RNA-binding
proteins and quells plant immunity. Nature 447, 284–288.
Cell Host & Microbe
Review
Gimenez-Ibanez, S., Hann, D.R., Ntoukakis, V., Petutschnig, E., Lipka, V., and
Rathjen, J.P. (2009). AvrPtoB targets the LysM receptor kinase CERK1 to
promote bacterial virulence on plants. Curr. Biol. 19, 423–429.
Godfrey, D., Böhlenius, H., Pedersen, C., Zhang, Z., Emmersen, J., and
Thordal-Christensen, H. (2010). Powdery mildew fungal effector candidates
share N-terminal Y/F/WxC-motif. BMC Genomics 11, 317.
Göhre, V., Spallek, T., Häweker, H., Mersmann, S., Mentzel, T., Boller, T., de
Torres, M., Mansfield, J.W., and Robatzek, S. (2008). Plant pattern-recognition
receptor FLS2 is directed for degradation by the bacterial ubiquitin ligase
AvrPtoB. Curr. Biol. 18, 1824–1832.
Guo, M., Tian, F., Wamboldt, Y., and Alfano, J.R. (2009). The majority of the
type III effector inventory of Pseudomonas syringae pv. tomato DC3000 can
suppress plant immunity. Mol. Plant Microbe Interact. 22, 1069–1080.
He, P., Chintamanani, S., Chen, Z., Zhu, L., Kunkel, B.N., Alfano, J.R., Tang, X.,
and Zhou, J.M. (2004). Activation of a COI1-dependent pathway in Arabidopsis
by Pseudomonas syringae type III effectors and coronatine. Plant J. 37,
589–602.
He, P., Shan, L., Lin, N.C., Martin, G.B., Kemmerling, B., Nürnberger, T., and
Sheen, J. (2006). Specific bacterial suppressors of MAMP signaling upstream
of MAPKKK in Arabidopsis innate immunity. Cell 125, 563–575.
Heese, A., Hann, D.R., Gimenez-Ibanez, S., Jones, A.M., He, K., Li, J.,
Schroeder, J.I., Peck, S.C., and Rathjen, J.P. (2007). The receptor-like kinase
SERK3/BAK1 is a central regulator of innate immunity in plants. Proc. Natl.
Acad. Sci. USA 104, 12217–12222.
Hemetsberger, C., Herrberger, C., Zechmann, B., Hillmer, M., and Doehle-
mann, G. (2012). The Ustilago maydis effector Pep1 suppresses plant
immunity by inhibition of host peroxidase activity. PLoS Pathog. 8,
e1002684. http://dx.doi.org/10.1371/journal.ppat.1002684.
Hirano, S.S., and Upper, C.D. (2000). Bacteria in the leaf ecosystem with
emphasis on Pseudomonas syringae-a pathogen, ice nucleus, and epiphyte.
Microbiol. Mol. Biol. Rev. 64, 624–653.
Hoch, H.C., Staples, R.C., Whitehead, B., Comeau, J., and Wolf, E.D. (1987).
Signaling for growth orientation and cell differentiation by surface topography
in uromyces. Science 235, 1659–1662.
Hogenhout, S.A., Van der Hoorn, R.A., Terauchi, R., and Kamoun, S. (2009).
Emerging concepts in effector biology of plant-associated organisms. Mol.
Plant Microbe Interact. 22, 115–122.
Horbach, R., Navarro-Quesada, A.R., Knogge, W., and Deising, H.B. (2011).
When and how to kill a plant cell: infection strategies of plant pathogenic fungi.
J. Plant Physiol. 168, 51–62.
Howlett, B.J. (2006). Secondary metabolite toxins and nutrition of plant path-
ogenic fungi. Curr. Opin. Plant Biol. 9, 371–375.
Hua, D., Wang, C., He, J., Liao, H., Duan, Y., Zhu, Z., Guo, Y., Chen, Z., and
Gong, Z. (2012). A plasma membrane receptor kinase, GHR1, mediates
abscisic acid- and hydrogen peroxide-regulated stomatal movement in
Arabidopsis. Plant Cell 24, 2546–2561.
Hückelhoven, R. (2007). Cell wall-associated mechanisms of disease resis-
tance and susceptibility. Annu. Rev. Phytopathol. 45, 101–127.
Huffaker, A., Pearce, G., and Ryan, C.A. (2006). An endogenous peptide signal
in Arabidopsis activates components of the innate immune response. Proc.
Natl. Acad. Sci. USA 103, 10098–10103.
Huynh, T.V., Dahlbeck, D., and Staskawicz, B.J. (1989). Bacterial blight of
soybean: regulation of a pathogen gene determining host cultivar specificity.
Science 245, 1374–1377.
Jabs, T., Tschope, M., Colling, C., Hahlbrock, K., and Scheel, D. (1997).
Elicitor-stimulated ion fluxes and O2- from the oxidative burst are essential
components in triggering defense gene activation and phytoalexin synthesis
in parsley. Proc. Natl. Acad. Sci. USA 94, 4800–4805.
Jelenska, J., Yao, N., Vinatzer, B.A., Wright, C.M., Brodsky, J.L., and Green-
berg, J.T. (2007). A J domain virulence effector of Pseudomonas syringae
remodels host chloroplasts and suppresses defenses. Curr. Biol. 17, 499–508.
Jeong, B.R., Lin, Y., Joe, A., Guo, M., Korneli, C., Yang, H., Wang, P., Yu, M.,
Cerny, R.L., Staiger, D., et al. (2011). Structure function analysis of an ADP-
ribosyltransferase type III effector and its RNA-binding target in plant immu-
nity. J. Biol. Chem. 286, 43272–43281.
Jones, J.D., and Dangl, J.L. (2006). The plant immune system. Nature 444,
323–329.
Kaku, H., Nishizawa, Y., Ishii-Minami, N., Akimoto-Tomiyama, C., Dohmae, N.,
Takio, K., Minami, E., and Shibuya, N. (2006). Plant cells recognize chitin frag-
ments for defense signaling through a plasma membrane receptor. Proc. Natl.
Acad. Sci. USA 103, 11086–11091.
Kale, S.D., Gu, B., Capelluto, D.G., Dou, D., Feldman, E., Rumore, A., Arre-
dondo, F.D., Hanlon, R., Fudal, I., Rouxel, T., et al. (2010). External lipid PI3P
mediates entry of eukaryotic pathogen effectors into plant and animal host
cells. Cell 142, 284–295.
Kamoun, S. (2006). A catalogue of the effector secretome of plant pathogenic
oomycetes. Annu. Rev. Phytopathol. 44, 41–60.
Kay, S., Hahn, S., Marois, E., Hause, G., and Bonas, U. (2007). A bacterial
effector acts as a plant transcription factor and induces a cell size regulator.
Science 318, 648–651.
Kelley, B.S., Lee, S.J., Damasceno, C.M., Chakravarthy, S., Kim, B.D., Martin,
G.B., and Rose, J.K. (2010). A secreted effector protein (SNE1) from Phytoph-
thora infestans is a broadly acting suppressor of programmed cell death. Plant
J. 62, 357–366.
Khang, C.H., Berruyer, R., Giraldo, M.C., Kankanala, P., Park, S.Y., Czymmek,
K., Kang, S., and Valent, B. (2010). Translocation of Magnaporthe oryzae effec-
tors into rice cells and their subsequent cell-to-cell movement. Plant Cell 22,
1388–1403.
Kim, H.S., Desveaux, D., Singer, A.U., Patel, P., Sondek, J., and Dangl, J.L.
(2005). The Pseudomonas syringae effector AvrRpt2 cleaves its C-terminally
acylated target, RIN4, from Arabidopsis membranes to block RPM1 activation.
Proc. Natl. Acad. Sci. USA 102, 6496–6501.
Kim, J.-G., Li, X., Roden, J.A., Taylor, K.W., Aakre, C.D., Su, B., Lalonde, S.,
Kirik, A., Chen, Y., Baranage, G., et al. (2009). Xanthomonas T3S effector
XopN suppresses PAMP-triggered immunity and interacts with a tomato atyp-
ical receptor-like kinase and TFT1. Plant Cell 21, 1305–1323.
Kleemann, J., Rincon-Rivera, L.J., Takahara, H., Neumann, U., van Themaat,
E.V., van der Does, H.C., Hacquard, S., Stüber, K., Will, I., Schmalenbach, W.,
et al. (2012). Sequential delivery of host-induced virulence effectors by appres-
soria and intracellular hyphae of the phytopathogen Colletotrichum higginsia-
num. PLoS Pathog. 8, e1002643. http://dx.doi.org/10.1371/journal.ppat.
1002643.
Kwon, C., Neu, C., Pajonk, S., Yun, H.S., Lipka, U., Humphry, M., Bau, S.,
Straus, M., Kwaaitaal, M., Rampelt, H., et al. (2008). Co-option of a default
secretory pathway for plant immune responses. Nature 451, 835–840.
Lacombe, S., Rougon-Cardoso, A., Sherwood, E., Peeters, N., Dahlbeck, D.,
van Esse, H.P., Smoker, M., Rallapalli, G., Thomma, B.P., Staskawicz, B.,
et al. (2010). Interfamily transfer of a plant pattern-recognition receptor confers
broad-spectrum bacterial resistance. Nat. Biotechnol. 28, 365–369.
Laluk, K., Luo, H., Chai, M., Dhawan, R., Lai, Z., and Mengiste, T. (2011).
Biochemical and genetic requirements for function of the immune response
regulator BOTRYTIS-INDUCED KINASE1 in plant growth, ethylene signaling,
and PAMP-triggered immunity in Arabidopsis. Plant Cell 23, 2831–2849.
Lan, L., Deng, X., Zhou, J., and Tang, X. (2006). Genome-wide gene expression
analysis of Pseudomonas syringae pv. tomato DC3000 reveals overlapping
and distinct pathways regulated by hrpL and hrpRS. Mol. Plant Microbe
Interact. 19, 976–987.
Lee, S.W., Han, S.W., Sririyanum, M., Park, C.J., Seo, Y.S., and Ronald, P.C.
(2009). A type I-secreted, sulfated peptide triggers XA21-mediated innate
immunity. Science 326, 850–853.
Lee, J., Teitzel, G.M., Munkvold, K., del Pozo, O., Martin, G.B., Michelmore,
R.W., and Greenberg, J.T. (2012). Type III secretion and effectors shape the
survival and growth pattern of Pseudomonas syringae on leaf surfaces. Plant
Physiol. 158, 1803–1818.
Lin, N.C., and Martin, G.B. (2005). An avrPto/avrPtoB mutant of Pseudomonas
syringae pv. tomato DC3000 does not elicit Pto-mediated resistance and is
less virulent on tomato. Mol. Plant Microbe Interact. 18, 43–51.
Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc. 493

Liu, J., Elmore, J.M., Fuglsang, A.T., Palmgren, M.G., Staskawicz, B.J., and
Coaker, G. (2009). RIN4 functions with plasma membrane H+-ATPases to
regulate stomatal apertures during pathogen attack. PLoS Biol. 7,
e1000139. http://dx.doi.org/10.1371/journal.pbio.1000139.
Liu, J., Elmore, J.M., Lin, Z.J., and Coaker, G. (2011). A receptor-like cyto-
plasmic kinase phosphorylates the host target RIN4, leading to the activation
of a plant innate immune receptor. Cell Host Microbe 9, 137–146.
Liu, T., Liu, Z., Song, C., Hu, Y., Han, Z., She, J., Fan, F., Wang, J., Jin, C.,
Chang, J., et al. (2012). Chitin-induced dimerization activates a plant immune
receptor. Science 336, 1160–1164.
Lorang, J.M., Sweat, T.A., and Wolpert, T.J. (2007). Plant disease suscepti-
bility conferred by a ‘‘resistance’’ gene. Proc. Natl. Acad. Sci. USA 104,
14861–14866.
Lu, D., Wu, S., Gao, X., Zhang, Y., Shan, L., and He, P. (2010). A receptor-like
cytoplasmic kinase, BIK1, associates with a flagellin receptor complex to
initiate plant innate immunity. Proc. Natl. Acad. Sci. USA 107, 496–501.
Lu, D., Lin, W., Gao, X., Wu, S., Cheng, C., Avila, J., Heese, A., Devarenne, T.P.,
He, P., and Shan, L. (2011). Direct ubiquitination of pattern recognition
receptor FLS2 attenuates plant innate immunity. Science 332, 1439–1442.
Macho, A.P., Boutrot, F., Rathjen, J.P., and Zipfel, C. (2012). ASPARTATE
OXIDASE plays an important role in Arabidopsis stomatal immunity. Plant
Physiol. 159, 1845–1856.
Melotto, M., Underwood, W., Koczan, J., Nomura, K., and He, S.Y. (2006).
Plant stomata function in innate immunity against bacterial invasion. Cell
126, 969–980.
Mendgen, K., and Hahn, M. (2002). Plant infection and the establishment of
fungal biotrophy. Trends Plant Sci. 7, 352–356.
Mengiste, T. (2012). Plant immunity to necrotrophs. Annu. Rev. Phytopathol.
50, 267–294.
Mentlak, T.A., Kombrink, A., Shinya, T., Ryder, L.S., Otomo, I., Saitoh, H.,
Terauchi, R., Nishizawa, Y., Shibuya, N., Thomma, B.P., and Talbot, N.J.
(2012). Effector-mediated suppression of chitin-triggered immunity by magna-
porthe oryzae is necessary for rice blast disease. Plant Cell 24, 322–335.
Mersmann, S., Bourdais, G., Rietz, S., and Robatzek, S. (2010). Ethylene
signaling regulates accumulation of the FLS2 receptor and is required for the
oxidative burst contributing to plant immunity. Plant Physiol. 154, 391–400.
Miya, A., Albert, P., Shinya, T., Desaki, Y., Ichimura, K., Shirasu, K., Narusaka,
Y., Kawakami, N., Kaku, H., and Shibuya, N. (2007). CERK1, a LysM receptor
kinase, is essential for chitin elicitor signaling in Arabidopsis. Proc. Natl. Acad.
Sci. USA 104, 19613–19618.
Monaghan, J., and Zipfel, C. (2012). Plant pattern recognition receptor
complexes at the plasma membrane. Curr. Opin. Plant Biol. 15, 349–357.
Mukhtar, M.S., Carvunis, A.R., Dreze, M., Epple, P., Steinbrenner, J., Moore,
J., Tasan, M., Galli, M., Hao, T., Nishimura, M.T., et al.; European Union Effec-
toromics Consortium. (2011). Independently evolved virulence effectors
converge onto hubs in a plant immune system network. Science 333, 596–601.
Navarro, L., Dunoyer, P., Jay, F., Arnold, B., Dharmasiri, N., Estelle, M.,
Voinnet, O., and Jones, J.D. (2006). A plant miRNA contributes to antibacterial
resistance by repressing auxin signaling. Science 312, 436–439.
Nomura, K., Debroy, S., Lee, Y.H., Pumplin, N., Jones, J., and He, S.Y. (2006).
A bacterial virulence protein suppresses host innate immunity to cause plant
disease. Science 313, 220–223.
Nomura, K., Mecey, C., Lee, Y.N., Imboden, L.A., Chang, J.H., and He, S.Y.
(2011). Effector-triggered immunity blocks pathogen degradation of an
immunity-associated vesicle traffic regulator in Arabidopsis. Proc. Natl.
Acad. Sci. USA 108, 10774–10779.
Nühse, T.S., Peck, S.C., Hirt, H., and Boller, T. (2000). Microbial elicitors induce
activation and dual phosphorylation of the Arabidopsis thaliana MAPK 6. J.
Biol. Chem. 275, 7521–7526.
O’Connell, R.J., Thon, M.R., Hacquard, S., Amyotte, S.G., Kleemann, J.,
Torres, M.F., Damm, U., Buiate, E.A., Epstein, L., Alkan, N., et al. (2012).
Lifestyle transitions in plant pathogenic Colletotrichum fungi deciphered by
genome and transcriptome analyses. Nat. Genet. 44, 1060–1065.
494 Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc.
Cell Host & Microbe
Review
Oliva, R., Win, J., Raffaele, S., Boutemy, L., Bozkurt, T.O., Chaparro-Garcia,
A., Segretin, M.E., Stam, R., Schornack, S., Cano, L.M., et al. (2010). Recent
developments in effector biology of filamentous plant pathogens. Cell. Micro-
biol. 12, 1015.
Ottmann, C., Luberacki, B., Küfner, I., Koch, W., Brunner, F., Weyand, M.,
Mattinen, L., Pirhonen, M., Anderluh, G., Seitz, H.U., et al. (2009). A common
toxin fold mediates microbial attack and plant defense. Proc. Natl. Acad.
Sci. USA 106, 10359–10364.
Pugin, A., Frachisse, J.M., Tavernier, E., Bligny, R., Gout, E., Douce, R., and
Guern, J. (1997). Early events induced by the elicitor cryptogein in tobacco
cells: involvement of a plasma membrane NADPH oxidase and activation of
glycolysis and the pentose phosphate pathway. Plant Cell 9, 2077–2091.
Qutob, D., Kemmerling, B., Brunner, F., Küfner, I., Engelhardt, S., Gust, A.A.,
Luberacki, B., Seitz, H.U., Stahl, D., Rauhut, T., et al. (2006). Phytotoxicity
and innate immune responses induced by Nep1-like proteins. Plant Cell 18,
3721–3744.
Rafiqi, M., Ellis, J.G., Ludowici, V.A., Hardham, A.R., and Dodds, P.N. (2012).
Challenges and progress towards understanding the role of effectors in plant-
fungal interactions. Curr. Opin. Plant Biol. 15, 477–482.
Ranf, S., Eschen-Lippold, L., Pecher, P., Lee, J., and Scheel, D. (2011). Inter-
play between calcium signalling and early signalling elements during defence
responses to microbe- or damage-associated molecular patterns. Plant J. 68,
100–113.
Robatzek, S., Chinchilla, D., and Boller, T. (2006). Ligand-induced endocytosis
of the pattern recognition receptor FLS2 in Arabidopsis. Genes Dev. 20,
537–542.
Robert-Seilaniantz, A., Grant, M., and Jones, J.D. (2011). Hormone crosstalk in
plant disease and defense: more than just jasmonate-salicylate antagonism.
Annu. Rev. Phytopathol. 49, 317–343.
Roux, M., Schwessinger, B., Albrecht, C., Chinchilla, D., Jones, A., Holton, N.,
Malinovsky, F.G., Tör, M., de Vries, S., and Zipfel, C. (2011). The Arabidopsis
leucine-rich repeat receptor-like kinases BAK1/SERK3 and BKK1/SERK4 are
required for innate immunity to hemibiotrophic and biotrophic pathogens.
Plant Cell 23, 2440–2455.
Schornack, S., van Damme, M., Bozkurt, T.O., Cano, L.M., Smoker, M.,
Thines, M., Gaulin, E., Kamoun, S., and Huitema, E. (2010). Ancient class of
translocated oomycete effectors targets the host nucleus. Proc. Natl. Acad.
Sci. USA 107, 17421–17426.
Schulze, B., Mentzel, T., Jehle, A.K., Mueller, K., Beeler, S., Boller, T., Felix, G.,
and Chinchilla, D. (2010). Rapid heteromerization and phosphorylation of
ligand-activated plant transmembrane receptors and their associated kinase
BAK1. J. Biol. Chem. 285, 9444–9451.
Schulze-Lefert, P., and Panstruga, R. (2011). A molecular evolutionary concept
connecting nonhost resistance, pathogen host range, and pathogen specia-
tion. Trends Plant Sci. 16, 117–125.
Shang, Y., Li, X., Cui, H., He, P., Thilmony, R., Chintamanani, S., Zwiesler-
Vollick, J., Gopalan, S., Tang, X., and Zhou, J.M. (2006). RAR1, a central player
in plant immunity, is targeted by Pseudomonas syringae effector AvrB. Proc.
Natl. Acad. Sci. USA 103, 19200–19205.
Song, J., Win, J., Tian, M., Schornack, S., Kaschani, F., Ilyas, M., van der
Hoorn, R.A., and Kamoun, S. (2009). Apoplastic effectors secreted by two
unrelated eukaryotic plant pathogens target the tomato defense protease
Rcr3. Proc. Natl. Acad. Sci. USA 106, 1654–1659.
Spanu, P.D., Abbott, J.C., Amselem, J., Burgis, T.A., Soanes, D.M., Stüber, K.,
Ver Loren van Themaat, E., Brown, J.K., Butcher, S.A., Gurr, S.J., et al. (2010).
Genome expansion and gene loss in powdery mildew fungi reveal tradeoffs in
extreme parasitism. Science 330, 1543–1546.
Stein, M., Dittgen, J., Sánchez-Rodrı́guez, C., Hou, B.H., Molina, A., Schulze-
Lefert, P., Lipka, V., and Somerville, S. (2006). Arabidopsis PEN3/PDR8, an
ATP binding cassette transporter, contributes to nonhost resistance to inap-
propriate pathogens that enter by direct penetration. Plant Cell 18, 731–746.
Stergiopoulos, I., and de Wit, P.J. (2009). Fungal effector proteins. Annu. Rev.
Phytopathol. 47, 233–263.
Tang, X., Xiao, Y., and Zhou, J.M. (2006). Regulation of the type III
secretion system in phytopathogenic bacteria. Mol. Plant Microbe Interact.
19, 1159–1166.
Cell Host & Microbe
Review
Taylor, K.W., Kim, J.G., Su, X.B., Aakre, C.D., Roden, J.A., Adams, C.M., and
Mudgett, M.B. (2012). Tomato TFT1 is required for PAMP-triggered immunity
and mutations that prevent T3S effector XopN from binding to TFT1 attenuate
Xanthomonas virulence. PLoS Pathog. 8, e1002768. http://dx.doi.org/10.
1371/journal.ppat.1002768.
Thines, B., Katsir, L., Melotto, M., Niu, Y., Mandaokar, A., Liu, G., Nomura, K.,
He, S.Y., Howe, G.A., and Browse, J. (2007). JAZ repressor proteins are
targets of the SCF(COI1) complex during jasmonate signalling. Nature 448,
661–665.
Thomma, B.P., Van Esse, H.P., Crous, P.W., and De Wit, P.J. (2005).
Cladosporium fulvum (syn. Passalora fulva), a highly specialized plant path-
ogen as a model for functional studies on plant pathogenic Mycosphaerella-
ceae. Mol. Plant Pathol. 6, 379–393.
Tsuda, K., and Katagiri, F. (2010). Comparing signaling mechanisms engaged
in pattern-triggered and effector-triggered immunity. Curr. Opin. Plant Biol. 13,
459–465.
van den Burg, H.A., Harrison, S.J., Joosten, M.H., Vervoort, J., and de Wit, P.J.
(2006). Cladosporium fulvum Avr4 protects fungal cell walls against hydrolysis
by plant chitinases accumulating during infection. Mol. Plant Microbe Interact.
19, 1420–1430.
Veronese, P., Nakagami, H., Bluhm, B., Abuqamar, S., Chen, X., Salmeron, J.,
Dietrich, R.A., Hirt, H., and Mengiste, T. (2006). The membrane-anchored
BOTRYTIS-INDUCED KINASE1 plays distinct roles in Arabidopsis resistance
to necrotrophic and biotrophic pathogens. Plant Cell 18, 257–273.
Vinatzer, B.A., Jelenska, J., and Greenberg, J.T. (2005). Bioinformatics
correctly identifies many type III secretion substrates in the plant pathogen
Pseudomonas syringae and the biocontrol isolate P. fluorescens SBW25.
Mol. Plant Microbe Interact. 18, 877–888.
Wan, J., Zhang, X.C., Neece, D., Ramonell, K.M., Clough, S., Kim, S.Y.,
Stacey, M.G., and Stacey, G. (2008). A LysM receptor-like kinase plays a
critical role in chitin signaling and fungal resistance in Arabidopsis. Plant Cell
20, 471–481.
Wang, Y., Li, J., Hou, S., Wang, X., Li, Y., Ren, D., Chen, S., Tang, X., and Zhou,
J.M. (2010). A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabi-
dopsis mitogen-activated protein kinase kinases. Plant Cell 22, 2033–2044.
Wang, Q., Han, C., Ferreira, A.O., Yu, X., Ye, W., Tripathy, S., Kale, S.D., Gu,
B., Sheng, Y., Sui, Y., et al. (2011). Transcriptional programming and functional
interactions within the Phytophthora sojae RXLR effector repertoire. Plant Cell
23, 2064–2086.
Whisson, S.C., Boevink, P.C., Moleleki, L., Avrova, A.O., Morales, J.G., Gilroy,
E.M., Armstrong, M.R., Grouffaud, S., van West, P., Chapman, S., et al. (2007).
A translocation signal for delivery of oomycete effector proteins into host plant
cells. Nature 450, 115–118.
Wildermuth, M.C., Dewdney, J., Wu, G., and Ausubel, F.M. (2001). Isochoris-
mate synthase is required to synthesize salicylic acid for plant defence. Nature
414, 562–565.
Wilton, M., Subramaniam, R., Elmore, J., Felsensteiner, C., Coaker, G., and
Desveaux, D. (2010). The type III effector HopF2Pto targets Arabidopsis
RIN4 protein to promote Pseudomonas syringae virulence. Proc. Natl. Acad.
Sci. USA 107, 2349–2354.
Xiang, T., Zong, N., Zou, Y., Wu, Y., Zhang, J., Xing, W., Li, Y., Tang, X., Zhu, L.,
Chai, J., and Zhou, J.M. (2008). Pseudomonas syringae effector AvrPto blocks
innate immunity by targeting receptor kinases. Curr. Biol. 18, 74–80.
Xiang, T., Zong, N., Zhang, J., Chen, J., Chen, M., and Zhou, J.M. (2011). BAK1
is not a target of the Pseudomonas syringae effector AvrPto. Mol. Plant
Microbe Interact. 24, 100–107.
Xing, W., Zou, Y., Liu, Q., Liu, J., Luo, X., Huang, Q., Chen, S., Zhu, L., Bi, R.,
Hao, Q., et al. (2007). The structural basis for activation of plant immunity by
bacterial effector protein AvrPto. Nature 449, 243–247.
Zeng, W., and He, S.Y. (2010). A prominent role of the flagellin receptor
FLAGELLIN-SENSING2 in mediating stomatal response to Pseudomonas
syringae pv tomato DC3000 in Arabidopsis. Plant Physiol. 153, 1188–1198.
Zeng, L., Velásquez, A.C., Munkvold, K.R., Zhang, J., and Martin, G.B. (2011).
A tomato LysM receptor-like kinase promotes immunity and its kinase activity
is inhibited by AvrPtoB. Plant J. 69, 92–103.
Zhang, J., Shao, F., Li, Y., Cui, H., Chen, L., Li, H., Zou, Y., Long, C., Lan, L.,
Chai, J., et al. (2007). A Pseudomonas syringae effector inactivates MAPKs
to suppress PAMP-induced immunity in plants. Cell Host Microbe 1, 175–185.
Zhang, J., Li, W., Xiang, T., Liu, Z., Laluk, K., Ding, X., Zou, Y., Gao, M., Zhang,
X., Chen, S., et al. (2010). Receptor-like cytoplasmic kinases integrate
signaling from multiple plant immune receptors and are targeted by a
Pseudomonas syringae effector. Cell Host Microbe 7, 290–301.
Zipfel, C., Robatzek, S., Navarro, L., Oakeley, E.J., Jones, J.D., Felix, G., and
Boller, T. (2004). Bacterial disease resistance in Arabidopsis through flagellin
perception. Nature 428, 764–767.
Cell Host & Microbe 12, October 18, 2012 ª2012 Elsevier Inc. 495