Secondary Metabolites

agronomy
Review
Secondary Metabolites, Other Prospective Substances, and
Alternative Approaches That Could Promote Resistance against
Phytophthora infestans
Hana Dufková 1 , Marie Greplová 2 , Romana Hampejsová 2 , Marharyta Kuzmenko 1 , Ervín Hausvater 2 ,
Břetislav Brzobohatý 1 and Martin Černý 1, *
1 Department of Molecular Biology and Radiobiology, Faculty of AgriSciences, Mendel University in Brno,
61300 Brno, Czech Republic; dufkova.ha1@gmail.com (H.D.); xkuzmenk@mendelu.cz (M.K.);
brzoboha@ibp.cz (B.B.)
2 Potato Research Institute, Ltd., 58001 Havlíčkův Brod, Czech Republic; greplova@vubhb.cz (M.G.);
hampejsova@vubhb.cz (R.H.); hausvater@vubhb.cz (E.H.)
* Correspondence: martincerny83@gmail.com; Tel.: +420-545-133-374
Abstract: Potato (Solanum tuberosum) is a valuable staple crop that provides nutrition for a large
part of the human population around the world. However, the domestication process reduced its
resistance to pests and pathogens. Phytophthora infestans, the causal agent of late blight disease, is the
most destructive pathogen of potato plants. Considerable efforts have been made to develop late
blight-resistant potato cultivars, but the success has been limited and present-day potato production
requires the extensive use of fungicides. In this review, we summarize known sources of late blight
resistance and obstacles in P. infestans control. We outline the problematic aspects of chemical
treatment, the possible use of biological control, and available resources of natural resistance in wild
Solanum accessions. We focus on prospective putative markers of resistance that are often overlooked
in genome-centered studies, including secondary metabolites from alkaloid, phenylpropanoid, and
Citation: Dufková, H.; Greplová, M.; terpenoid classes, lipids, proteins, and peptides. We discuss the suitability of these molecules for
Hampejsová, R.; Kuzmenko, M.; marker-assisted selection and the possibility of increasing the speed of conventional breeding of more
Hausvater, E.; Brzobohatý, B.; Černý, resilient cultivars.
M. Secondary Metabolites, Other
Prospective Substances, and
Keywords: late blight; breeding; molecular markers; mQTL; lipids; secondary metabolites; proteins;
Alternative Approaches That Could
biological control
Promote Resistance against
Phytophthora infestans. Agronomy 2023,
13, 1822. https://doi.org/10.3390/
agronomy13071822
1. Introduction
Academic Editors: Andreia
Archeological evidence indicates that wild potato species were part of the human diet
S. Loureiro and Inês Diniz
more than 10,000 years ago [1], and potato domestication is believed to date back around
Received: 9 June 2023 8000 years to the Andean region of the present-day states of Peru and Bolivia [2]. The
Revised: 1 July 2023 commonly known potato (Solanum tuberosum) was introduced to Europe in the late 16th
Accepted: 7 July 2023 century. It was rapidly spread across the world by European colonial powers, becoming
Published: 9 July 2023 a major staple in many regions (Figure 1). Potato cultivation is said to have contributed
to the industrialization of Europe by nourishing and boosting the population in the 17th
and 18th centuries, and the failure of potato production caused by Phytophthora infestans
led to the infamous Great Famine in Ireland [3]. Today, annual potato production has
Copyright: © 2023 by the authors.
reached 360 million tons (Food and Agriculture Organization of the United Nations; https:
Licensee MDPI, Basel, Switzerland.
//www.fao.org/; accessed on 10 December 2022). Potato is a more efficient crop than wheat,
This article is an open access article
with higher yields and lower demands on water consumption [4]. However, a part of its
distributed under the terms and
domestication included a decrease in protective toxic compounds such as glycoalkaloids [5].
conditions of the Creative Commons
Attribution (CC BY) license (https://
That has reduced its resistance to pests and pathogens, and potato is one of the most
creativecommons.org/licenses/by/
fungicide-dependent crops in the world [6]. It is affected by insects, nematodes, fungi,
4.0/).
oomycetes, bacteria, and viruses, resulting in an estimated annual yield loss of about
Agronomy 2023, 13, 1822. https://doi.org/10.3390/agronomy13071822 https://www.mdpi.com/journal/agronomy

Agronomy 2023, 13, x FOR PEER REVIEW 2 of 25
Agronomy 2023, 13, 1822 2 of 23
fungi, oomycetes, bacteria, and viruses, resulting in an estimated annual yield loss of
about 20% [7]. P. infestans (late blight), Alternaria solani (early blight), Streptomyces scabies
20% [7]. P. scab),
(common infestans (late blight),
Rhizoctonia Alternaria
solani solani (early
(black scurf), blight),
Ralstonia Streptomyces
solanacearum scabies wilt),
(bacterial (commonand
scab), Rhizoctonia solani (black scurf), Ralstonia solanacearum (bacterial wilt), and PVYin-N
PVY (tuber necrosis) remain the most important reemerging pathogens in the potato
N
(tuber
dustrynecrosis)
worldwide remain
[8]. the most important reemerging pathogens in the potato industry
worldwide [8].
Figure 1.
Figure 1. Potato—a
Potato—a staple crop
staple throughout
crop throughoutthe world. (a) Origin
the world. of potatoes
(a) Origin and early
of potatoes spread
and earlythrough-
spread
out the world by Spanish, English, Portuguese, and Dutch (blue); P. infestans infestation and its rapid
throughout the world by Spanish, English, Portuguese, and Dutch (blue); P. infestans infestation
spread (red) [3,9,10]. The map gradient corresponds to the mean annual production in the last 20 years.
and its rapid spread (red) [3,9,10]. The map gradient corresponds to the mean annual production
(b) Increase in potato yield in 60 years (https://www.fao.org/, accessed on 10 December 2022).
in the last 20 years. (b) Increase in potato yield in 60 years (https://www.fao.org/, accessed on
10 December
It took 2022).
more than a century to establish potatoes as a crop of global importance in
Europe. In contrast,
It took more than theaspread
century of to
late blight occurred
establish potatoeswithin decades
as a crop (Figure
of global 1), and only
importance in
Europe. In contrast, the spread of late blight occurred within decades (Figure 1), and onlyin
a few recorded crop failures have been as devastating as those caused by this pathogen a
the 1840s.
few recordedThecrop
geographic
failures origin of P.as
have been infestans is disputed,
devastating as thosewith some
caused bystudies indicating
this pathogen in
a Mexican
the 1840s. Thecenter of origin origin
geographic [11] and some
of P. providing
infestans evidence
is disputed, withforsome
a region in the
studies Andean
indicating
highlands [12]. Interestingly, the original FAM-1 genotype went extinct
a Mexican center of origin [11] and some providing evidence for a region in the Andean and has been re-
placed by more
highlands aggressive lineages
[12]. Interestingly, [9]. The
the original rapid genotype
FAM-1 evolution went
of thisextinct
pathogenand remains
has beena
major threat
replaced to global
by more food security,
aggressive lineagesand [9]. significant yield loss results
The rapid evolution in annual remains
of this pathogen economic a
losses threat
major estimated at billions
to global of euros and
food security, [13].significant
This review summarizes
yield loss resultscurrent strategies
in annual economicand
limitations
losses for controlling
estimated at billionspotato late[13].
of euros blight. It review
This provides insight intocurrent
summarizes P. infestans resistance
strategies and
and discusses novel approaches and molecular markers that could be utilized
limitations for controlling potato late blight. It provides insight into P. infestans resistance to speed up
the breeding
and discussesprocess of new resistant
novel approaches cultivars.markers that could be utilized to speed up
and molecular
the breeding process of new resistant cultivars.
2. Phytophthora infestans
2. Phytophthora
Phytophthorainfestans
(from the Greek for plant-destroyer) is a globally distributed genus of
Phytophthora
fungus-like (from that
oomycetes the Greek
cause for plant-destroyer)
agricultural is a globally
and ecological plantdistributed genus
diseases [14]. of
It in-
fungus-like
cludes moreoomycetes
than 200 taxathat distributed
cause agricultural
across and
twelve ecological
clades, plant diseases [14].
and pathogens withIt aincludes
signifi-
more than 200impact
cant negative taxa distributed
on agricultural across twelve clades,
production and in
are found pathogens
several ofwith a significant
these. For exam-
negative impactbelongs
ple, P. infestans on agricultural
to clade 1,production
together withareP. found in several
parasitica, of these.
P. nicotianae, andFor
P. example,
cactorum.
P. infestans belongs to clade 1, together with P. parasitica, P. nicotianae,
The second clade includes P. capsici, and the representants of clade 4 are the pathogens and P. cactorum. P.
The second clade includes P. capsici, and the representants of clade 4
megakarya and P. palmivora. Finally, P. sojae and P. cinnamomi are found in clade 7 [15]. P.are the pathogens
P. megakarya
infestans wasandfirstP.described
palmivora.byFinally,
HeinrichP. sojae
Anton and deP.Bary,
cinnamomi are found
who studied the in cladedisease
potato 7 [15].
P. infestans was first described by Heinrich Anton de Bary, who studied
responsible for the Great Irish Famine [16]. It is an obligate hemibiotrophic pathogen that the potato disease
responsible
attacks livingfor the Great
tissues (leaves,Irish Famine
stems, [16].of It
tubers) theisSolanaceae
an obligate hemibiotrophic
plant pathogen
family [17]. Most infec-
that attacks living tissues (leaves, stems, tubers) of the Solanaceae plant
tions during a season are initiated by rapid asexual reproduction, and P. infestans can family [17]. Most be
infections during a season are initiated by rapid asexual reproduction,
spread aerially through asexual sporangia. Spores enter leaves and stems through natural and P. infestans
can be spread aerially through asexual sporangia. Spores enter leaves and stems through
openings (e.g., stomata), buds, wounds, or by direct cuticle and epidermis disruption, us-
natural openings (e.g., stomata), buds, wounds, or by direct cuticle and epidermis disrup-
ing a slicing mechanism called a naifu invasion [18]. The long-distance movement and
tion, using a slicing mechanism called a naifu invasion [18]. The long-distance movement
spreading of the pathogen are mainly anthropomorphic, due to global trade and the un-
and spreading of the pathogen are mainly anthropomorphic, due to global trade and the
intended transport of infected tubers for use as seed potatoes [19]. P. infestans may
unintended transport of infected tubers for use as seed potatoes [19]. P. infestans may
overwinter in tubers which then serve as the primary inoculum in the field. In parallel,
Agronomy 2023, 13, 1822 3 of 23
contact between infected tubers and healthy tubers in storage promotes infection spread,
and the careful removal of infected tubers before storage, forced air ventilation, controlled
temperature and humidity, and disinfectants are commonly used to protect the harvest and
mitigate disease transmission [20]. P. infestans takes up nutrients from living plant tissues
until the terminal phase of infection occurs. This phase is associated with host necrosis and
pathogen sporulation, which can occur as early as three days after leaf infection [21]. Rapid
sporangia production and its long-distance dispersion by the wind result in the ability of
P. infestans to destroy unprotected crop vegetation in a few weeks [22,23]. Asexual zoospores
are essential for population growth. However, due to the spread of alternative mat-
ing types (A1 and A2), the co-occurrence of both mating types and sexual reproduc-
tion is also possible, presenting a risk of the emergence of more aggressive P. infestans
genotypes [24–26]. The mating in P. infestans leads to the production of thick-walled
oospores that serve as survival structures and additional sources of inoculum [27]. Sexual
reproduction is area-specific and seems to be preferred under stress conditions. Interest-
ingly, the most aggressive known P. infestans isolates are triploid clonal lineages US-1 and
13_A2, and under stress the triploid genotype can change to a diploid one [28].
3. Resistance to P. infestans
3.1. Plant Innate Immunity
Plants have evolved several layers of defense to resist pathogen attacks. In addition to
a passive defense based on physical barriers and chemical composition, plants have evolved
active defense mechanisms. In the classical model of plant–pathogen interaction (Figure 2),
pattern-triggered immunity (PTI) is activated by recognizing molecular patterns associated
with pathogens or damage. Phytophthora produces several unique compounds that are
recognized by plant receptors, including cysteine-rich proteins elicitins, eicosapolyenoic
acids, and ß-glucans released from the cell wall of oomycetes by plant glucanases [29].
Successful PTI leads to ROS burst and hypersensitive response, the expression of de-
fense genes, callose deposition, and the accumulation of protective secondary metabolites.
P. infestans produces effectors that block PTI responses or stimulate plant susceptibility fac-
tors [21,30–32]. In turn, plants have evolved resistance proteins (R-proteins) that facilitate
effector recognition and effector-triggered immunity (ETI) activation, often resulting in a
hypersensitive reaction [33]. The PTI and the ETI are associated with so-called qualitative
(vertical) and quantitative (horizontal) resistance, respectively. Qualitative resistance is, by
definition, based on a single major resistance gene (R gene), providing efficient protection
against a pathogen genotype producing specific protein. The durability of R gene-based
resistance is limited by multiple obstacles, including the sheer number of effector proteins
that are evolving and increasing the pathogen’s ability to escape recognition mediated
by R proteins and establish a successful infection. The best-described virulent effectors
are RXLR (conserved Arg-Xaa-Leu-Arg motifs in their N-terminal sequence) and CRN
proteins (CRinkle and Necrosis phenotype). These proteins are secreted by Phytophthora
and are destined to be translocated and function inside host cells [34]. P. infestans encodes
approximately 560 and 190 RXLR and CRN effectors, respectively, and of these roughly one
half are assumed to be important for the infection [35–37]. The effectors that are recognized
by R proteins and trigger ETI are referred to as avirulence proteins, and a mutation in the
corresponding genes and gene silencing enable Phytophthora to escape the recognition [38].
P. infestans has an enormous capacity to adapt to plant defense mechanisms. Continuous
and rapid changes in P. infestans populations caused by sexual recombination, persistent
oospores, rapid asexual reproduction, genome plasticity, and international migration have
significant implications for the rapid evolution of pathogen virulence, unbalancing the
arms race in its favor. Consequently, cultivated potatoes suffer from reemerging late blight
epidemics [22].
In contrast to qualitative, quantitative resistance is the combined result of interactions
between multiple genes referred to as quantitative trait loci (QTLs). These genes/proteins
play only a minor role in defense, but the resulting additive effect of a large number
Agronomy 2023, 13, 1822 4 of 23

In contrast to qualitative, quantitative resistance is the combined result of interactions
between multiple genes referred to as quantitative trait loci (QTLs). These genes/proteins
play only a minor role in defense, but the resulting additive effect of a large number of
of components
components withwith minor
minor individual
individual influences
influences promotes
promotes resistance.
resistance. Plants do Plants
not showdocom-
not
show complete resistance, but the process is more robust and is usually not pathogen-
plete resistance, but the process is more robust and is usually not pathogen-specific [39–42].
specific
The number[39–42]. The number
of putative QTLsof putativeisQTLs
identified identified
steadily is steadily
increasing [43–46],increasing [43–46],
but the molecular
but the molecular mechanisms underlying the resulting resistance are
mechanisms underlying the resulting resistance are far from understood. An example far from under-
of a
stood. An example of a known mechanism of quantitative resistance to P. infestans is cell
known mechanism of quantitative resistance to P. infestans is cell wall thickening due to the
wall thickening due to the deposition of hydroxycinnamic acid amides, flavonoids, and
deposition of hydroxycinnamic acid amides, flavonoids, and alkaloids [47].
alkaloids [47].
It should be noted that the differences between quantitative and qualitative resistance
It should be noted that the differences between quantitative and qualitative resistance
are not as concrete as initially thought. Many QTLs contain clusters of known R gene
are not as concrete as initially thought. Many QTLs contain clusters of known R gene
homologs that seem to be involved in the QTL effect (e.g., [48]). For example, several R
homologs that seem to be involved in the QTL effect (e.g., [48]). For example, several R
genes identified in wild potato species confer broad-spectrum resistance [49].
genes identified in wild potato species confer broad-spectrum resistance [49].
Figure 2. The
Figure Thesimplified
simplifiedmodel
modelof of
potato immune
potato responses
immune to P.to
responses infestans. PAMP,PAMP,
P. infestans. pathogen-associ-
pathogen-
ated molecular
associated pattern;
molecular DAMP,
pattern; damage-associated
DAMP, damage-associatedmolecular pattern;
molecular E, pathogen’s
pattern; effector;
E, pathogen’s R,
effec-
plant’s R protein; PRR, pattern-recognition receptor; PTI, pattern-triggered immunity;
tor; R, plant’s R protein; PRR, pattern-recognition receptor; PTI, pattern-triggered immunity; ETI,ETI, effector-
triggered immunity; RRP, resistance-related proteins; RRM, resistance-related metabolites. Refer-
effector-triggered immunity; RRP, resistance-related proteins; RRM, resistance-related metabolites.
ences: 1 [31], 2 [50], 3 [29], 4 [51], 5 [30], 6 [52].
References: 1 [31], 2 [50], 3 [29], 4 [51], 5 [30], 6 [52].
3.2. Chemical
3.2. Chemical Treatment
Treatment
Late blight
Late blight isis predominantly
predominantly managed
managed by the continuous use of fungicides, and ex-
perimental
perimental evidence indicates that
that 20–60%
20–60% of of annual
annualproduction
productionwould wouldbebelostlostwithout
withoutit
it[53].
[53].The useuse
The of of
chemicals
chemicals against P. infestans
against P. infestansdates to the
dates latelate
to the 19th19thcentury, with
century, the the
with ap-
plication of of
application thethe
Bordeaux
Bordeaux mixture
mixture(CuSO 4, CaO)
(CuSO 4 , CaO)discovered
discoveredby Pierre-Marie-Alexis
by Pierre-Marie-Alexis Mil-
lardet in 1882.
Millardet Its application
in 1882. was gradually
Its application replacedreplaced
was gradually by the nextby generations of fungicides
the next generations of
because copper
fungicides because is persistent
copper isinpersistent
the environment and phytotoxic,
in the environment and butphytotoxic,
it is still used
butinitor-
is
ganic
still usedagriculture
in organic [54]. The European
agriculture register
[54]. The in 2022register
European listed 37in fungicides
2022 listedand fungicidal
37 fungicides
and fungicidal
mixtures, mixtures,both
including including both preventative
preventative and curativeand curative
compoundscompounds (EuroB-
(EuroBlight,
light, https://agro.au.dk/forskning/internationale-platforme/euroblight/,
https://agro.au.dk/forskning/internationale-platforme/euroblight/, accessed on accessed on
10 Decem-
10
berDecember
2022), and 2022),
someand some commonly
commonly used compounds
used compounds are listed inareFigure
listed3.inTraditional
Figure 3. Tradi-
treat-
tional treatmentondepends
ment depends on preventive
preventive fungicides
fungicides applied appliedduring
regularly regularly during the
the growing growing
season, and
season, and theperiod
the treatment treatment period
depends ondepends
weatheron weather conditions
conditions and cultivar and cultivar resistance,
resistance, as well as
as well as fungicide
fungicide characteristics
characteristics and efficacy.and efficacy.
Readers Readers in
interested interested in these
these aspects andaspects and
the benefits
the benefits of precision agriculture in the fight against late blight are referred to the report
published by Yangxuan Liu et al. (2017) [55]. Preventive fungicides must be present before
infection, and only a selected few provide systemic protection [56]. More importantly,
Agronomy 2023, 13, 1822

of precision agriculture in the fight against late blight are referred to the report published
5 of 23
by Yangxuan Liu et al. (2017) [55]. Preventive fungicides must be present before infection,
and only a selected few provide systemic protection [56]. More importantly, P. infestans
has already evolved resistance to some fungicides [57], and strict resistance management
P. infestansare
measures hasrequired.
already evolved resistance of
The overexposure to target
some populations
fungicides [57], and strict fungicides
to single-site resistance
management measures are required. The overexposure of target populations to single-site
should be avoided [58]. A less effective but more environmentally friendly approach than
fungicides should be avoided [58]. A less effective but more environmentally friendly
a conventional fungicide is treatment with phosphite (e.g., KPO3). Interestingly, its appli-
approach than a conventional fungicide is treatment with phosphite (e.g., KPO3 ). Interest-
cation can reduce the dosage of fungicides without compromising protection against late
ingly, its application can reduce the dosage of fungicides without compromising protection
potato blight [59–61]. A similar effect was found with the direct application of phospho-
against late potato blight [59–61]. A similar effect was found with the direct application of
rous acid, when a significant reduction in the severity of the disease was observed even at
phosphorous acid, when a significant reduction in the severity of the disease was observed
half the recommended concentration of fungicides [62].
even at half the recommended concentration of fungicides [62].
Figure 3.
Figure Examplesofoffungicide
3.Examples fungicideused
usedfor
forthe
the control
control of of late
late blight.
blight. ForFor details,
details, see see references
references [63–67].
[63–67].
3.3. Biological
3.3. Biological Control
Control
The risk of acquired tolerance to fungicides and public demand to limit pesticide
The risk of acquired tolerance to fungicides and public demand to limit pesticide
applications have driven the search for alternative chemicals of natural origin and natural
applications have driven the search for alternative chemicals of natural origin and natural
enemies of the pathogen. The search has provided a large number of candidates, with
enemies of the pathogen. The search has provided a large number of candidates, with
some notable examples listed in Table 1. Promising targets are endophytes, microorganisms
some notable examples listed in Table 1. Promising targets are endophytes, microorgan-
growing within plants without causing apparent disease symptoms in their host [68–70].
isms growing within plants without causing apparent disease symptoms in their host [68–
The protective effect of these microbes can originate from different mechanisms, including
70]. The protective effect of these microbes can originate from different mechanisms,
a simple competition for nutrients and space, the production of antifungal compounds,
and the priming of the host’s defense mechanisms [71]. The direct application of living
microbes could have undesirable side effects on the plant host, the microflora, and the soil
environment. This can be avoided by the application of cell-free extracts [72,73]. On the
Agronomy 2023, 13, 1822 6 of 23
other hand, the metabolome of endophytes varies depending on their environment. There-
fore, an in vitro or ex planta production is unlikely to produce an identical composition of
compounds to that found in the natural environment [74]. In addition to microbial extracts,
a recent study showed that extracts of plants resistant to Phytophthora could be effective
protectants [75]. Interestingly, despite years of experimental evidence and numerous candi-
date biological agents, the transfer of in vitro and greenhouse results to the field has not
been very successful for late blight control. This is not surprising because biological control
is dependent on the environment, and both abiotic factors and indigenous microbes can
suppress its protective effects by limiting the growth of the biological agent or affecting
its effect [76]. Part of that problem could possibly be circumvented by exploiting natural
potato endophytes. A recent study isolated more than 200 endophytes from the healthy
roots of field-grown potatoes and showed that a significant portion of these microbes
manifested anti-oomycete activity [77].
Table 1. Representative biocontrol agents tested for late blight disease management.
Examples of
Organism Effect References
Biocontrol Agents
Xanthium strumarium, Lauris nobilis,
Salvia officinalis, Mycelial growth inhibition [73]
Styrax officinalis
Extracts
Mycelial growth inhibition,
Solanum habrochaites [75]
reduced disease progression
Willaertia magna C2c Maky Disease reduction [78]
Trichoderma virens reduced disease progression [72]
Pseudomonas strains isolated from the
Reduced disease progression [79]
rhizosphere and shoots of potato
Bacteria Bacillus subtilis Reduced disease progression [80]
Myxococcus fulvus Reduced disease progression [81]
Bacillus velezensis [77,82]
improved resistance
Fungal endophytes isolated from
Mycelial growth inhibition [69]
Solanum spp.
Fungi Fusarium oxysporum Induction of systemic resistance [83]
Fungal endophytes isolated from
Mycelial growth inhibition [68]
Espeletia spp.
Endophytes Phoma eupatorii [70]
infection prevention
3.4. Resistant Cultivars

3.4.1. Natural Resistance
The impact of late blight on yield can be avoided by using varieties that are less
sensitive to P. infestans or by very early bulking to escape late blight infection. However, as
illustrated in Figure 4, resistant cultivars represent only a minority in the list of registered
cultivars, and public demand requires the production of many traditional cultivars that
are not resistant. An extensive resource of resistance is hidden in more than 100 wild
potato species, with late blight resistance developed during the ages of host and pathogen
coevolution [84–88]. The number of recognized species resistant to Phytophthora has been
steadily growing, and both Solanum genotypes with foliar resistance and tuber resistance to
P. infestans have been identified [89–93]. Wild germplasms have been exploited in breeding
processes for a long time, including S. demissum, S. bulbocastanum, S. stoloniferum, and S.
verrucosum (as reviewed in [94]), and more than 70 Rpi genes have been identified and
mapped in 32 Solanum species [95]. However, only a minority of identified species resistant
to P. infestans can be directly used for resistance breeding in tetraploid potato cultivars
(2n = 4x = 48) without the manipulation of ploidy by chromosome doubling, unreduced
steadily growing, and both Solanum genotypes with foliar resistance and tuber resistance
to P. infestans have been identified [89–93]. Wild germplasms have been exploited in
breeding processes for a long time, including S. demissum, S. bulbocastanum, S. stoloniferum,
and S. verrucosum (as reviewed in [94]), and more than 70 Rpi genes have been identified
Agronomy 2023, 13, 1822 and mapped in 32 Solanum species [95]. However, only a minority of identified species 7 of 23
resistant to P. infestans can be directly used for resistance breeding in tetraploid potato
cultivars (2n = 4x = 48) without the manipulation of ploidy by chromosome doubling, un-
reduced gametes, bridge crosses, somatic fusions, or other means to circumvent hybridi-
gametes, bridge crosses, somatic fusions, or other means to circumvent hybridization
zation barriers [96].
barriers [96].
Figure4.4.Late
Figure Late blight
blight disease
disease resistance
resistance monitored
monitoredininpotato
potatovarieties registered
varieties in in
registered thethe
Czech Repub-
Czech Re-
lic. The disease rating classifies varieties into four groups, based on the disease rating
public. The disease rating classifies varieties into four groups, based on the disease rating scale scale 1–9:
susceptible (1–3), less susceptible (4–5), moderately resistant (6–7), and resistant (8–9) (Central In-
1–9: susceptible (1–3), less susceptible (4–5), moderately resistant (6–7), and resistant (8–9) (Central
stitute for Supervising and Testing in Agriculture, https://eagri.cz/public/web/en/ukzuz/por-
Institute for Supervising and Testing in Agriculture, https://eagri.cz/public/web/en/ukzuz/portal/
tal/plant-varieties/information-on-plant-varieties/results-of-testing-of-plant-varieties/, accessed on
plant-varieties/information-on-plant-varieties/results-of-testing-of-plant-varieties/,
15 November 2022). It should be noted that the level and type of cultivar resistance accessed on 15
can change
November 2022). It should be noted that the level and type of cultivar resistance can
across time and space [97], predominantly with the emergence of new Phytophthora genotypes. change across
time and space [97], predominantly with the emergence of new Phytophthora genotypes.
3.4.2. Traditional Breeding
3.4.2. Traditional Breeding
The introgression of durable resistance to Phytophthora into cultivated potatoes is a
The introgression of durable resistance to Phytophthora into cultivated potatoes is a
time-intensive process (Figure 5) and often ends in disappointment. The limiting factors
time-intensive process (Figure 5) and often ends in disappointment. The limiting factors
in late blight resistance breeding are not only the long breeding cycles and the genome of
in late blight resistance breeding are not only the long breeding cycles and the genome
cultivars that are highly heterozygous tetraploid plants. In fact, most of the resistant cul-
of cultivars that are highly heterozygous tetraploid plants. In fact, most of the resistant
tivars obtained
cultivars obtainedhadhadinsufficient table
insufficient oror
table processing quality
processing forfor
quality commercial
commercial success, or or
success, re-
resistance was soon lost due to the rapid evolution of the pathogen [98,99]. For example,a
sistance was soon lost due to the rapid evolution of the pathogen [98,99]. For example,
avery
very promising
promising introgression
introgression of of an
an RR gene
gene from
from S.S.demissum
demissumintointocultivated
cultivatedpotatoes
potatoes
started in the early twentieth century and took several decades. The resulting
started in the early twentieth century and took several decades. The resulting cultivar wascultivar was
soon found to be ineffective [100], and decades-long breeding procedures failed in only a
few growing seasons when new virulent races of P. infestans evaded resistance. The Sárpo
Mira cultivar is one of the few potato cultivars that has been reported to retain resistance
in the field for more than a decade. Its genetic origin has not been publicly disclosed,
but its genome contains a set of at least five different R genes that confer qualitative and
quantitative resistance to late blight [101–103]. It has been used in studies of late blight
resistance and as a source of resistance in conventional breeding [102,104]. On average,
the traditional potato breeding process takes more than ten years from the initial crossing
(Figure 5) to obtaining a new cultivar, but the process can take considerably more time due
to a laborious selection process, backcrossing, and the elimination of undesirable quality
traits [105]. The introgression of a single R gene from the wild species S. bulbocastanum
into the Bionica and Toluca potato cultivars took an astonishing 46 years [106]. Investment
in conventional breeding and multilateral collaboration can significantly improve the
throughput of the process, as exemplified by the Bioimpuls project that has been running
since 2009 and has provided a constant flow of breeding clones with introgressed resistance
genes [107].
due to a laborious selection process, backcrossing, and the elimination of undesirable
quality traits [105]. The introgression of a single R gene from the wild species S. bulbocas-
tanum into the Bionica and Toluca potato cultivars took an astonishing 46 years [106]. In-
vestment in conventional breeding and multilateral collaboration can significantly im-
prove the throughput of the process, as exemplified by the Bioimpuls project that has been
Agronomy 2023, 13, 1822 8 of 23
running since 2009 and has provided a constant flow of breeding clones with introgressed
resistance genes [107].
Figure 5. Simplified overview of the traditional breeding process. The illustration is based on the
Figure 5. Simplified overview of the traditional breeding process. The illustration is based on the
practice of Czech potato breeders and represents a standard process that does not require ploidy
practice of Czech potato breeders and represents a standard process that does not require ploidy
manipulation or backcrossing steps.
manipulation or backcrossing steps.
3.4.3. New Breeding Technologies for Potato Improvement

Modern genetic engineering techniques are more efficient and faster in introducing
resistance genes into susceptible cultivars than traditional breeding. These techniques
have been successfully used, especially in the pyramiding (stacking) of the R genes, to
improve both the durability and the level of resistance [39,95,108–117]. The GMO cultivars
were successful in field tests [106,116]. However, despite using only genes from wild
Solanum species crossable with cultivated potato varieties (a cisgenic approach), the global
ostracization of GMOs and legal restrictions have significantly limited the use of these
GMO cultivars. Interestingly, in addition to stacking resistance genes for more durable
resistance, transformation allows a successful late blight control based on the gene silencing
of susceptibility genes [118–120].
3.4.4. Somatic Hybridization

The cultivated potato was one of the first crops successfully cultured in vitro and
used to obtain somatic hybrids [121]. Somatic hybridization via protoplast electrofusion
Agronomy 2023, 13, 1822 9 of 23
enables the fast and robust production of potato breeding material. This method of genetic
manipulation is not subject to GMO legislation, and the resulting plants are not considered
genetically modified (Directive 2001/18/EC—Annex 1B). Somatic hybrids are generally
not suitable for cultivar trials but could be very useful as pre-breeding lines, especially to
overcome hybridization barriers, as documented in recent literature [111,122–126].
4. Marker-Assisted Selection
The breeding process is considerably accelerated by a cost-effective molecular marker-
assisted selection (MAS) diagnostic for both qualitative and quantitative traits. The ap-
proach to the detection of resistant genotypes is based on identified biomarkers that quali-
tatively occur only in resistant genotypes or are significantly more abundant in resistant
plants (compared to susceptible ones) [127]. MAS applied to preselected crosses in the
fourth year of the breeding cycle (Figure 5) could shorten the breeding process by at least
three years [87].
4.1. Genome-Based Analyses

Genomic techniques are powerful and robust tools for the detection of resistance
markers and are the dominant approach in MAS [128]. DNA markers have been widely
used in various breeding processes [45,129,130], and several have been developed to be
used in MAS for resistance to late blight [112,131]. These markers are based on dominant
R genes and identified QTLs, and the list of these is steadily increasing. For example, the
mapping of R genes belonging to the nucleotide-binding and leucine-rich repeat (NB-LRR)
family aided by resistance gene enrichment sequencing (RenSeq) identified more than
750 putative R genes in the reference genome of S. tuberosum [132]. A detailed list of
identified late-blight resistance genes has recently been summarized in an excellent review
article [95], and readers are referred to that source for further information.
4.2. Metabolome-Based Analyses

Genetic markers are associated with a trait of interest. Ideally, the marker originates
from the allelic variant of the gene that governs the desired phenotypic effect. However,
durable quantitative resistance is controlled by an intricate network of genes and other
regulatory elements. Some of these elements are involved in transcription regulation and
gene silencing, while others determine biochemical traits and metabolite production. These
genes provide an additive effect that is difficult to understand, but the corresponding
metabolome signatures are directly measurable and are often described as metabolic QTL
(mQTL) [133]. General applications of metabolomics in plant breeding have recently been
reviewed [134,135]. Here, we will discuss the potato metabolome and putative targets for
late blight resistance breeding. It is estimated that thousands of diverse metabolites are
synthesized by potato plants, but only a relatively small part of these are routinely identified
and quantified. For example, a recently published database of root, tuber, and banana crops
contains data for fewer than 100 metabolites of S. tuberosum [136]. Many recent studies had
a similar metabolome coverage in the mid-hundreds of identified metabolites [137–140].
Despite advances in the sensitivity of the metabolomic methods, the analyses are limited by
at least three factors: (i) dynamic concentration ranges and spatiotemporal changes in the
metabolome, (ii) the diversity in physicochemical properties of metabolites that necessitates
the use of complementary analytical workflows, and (iii) a large number of unidentified
metabolites. Untargeted metabolomics analyses allow for the measurement of both known
and unknown metabolites. Unknown metabolites (features) are characterized by unique
retention time, specific mass, and fragmentation spectra. In theory, these features could be
used as mQTLs for MAS but are usually excluded because the underlying mechanisms of
the observed phenotypes are lacking.
Identified resistance-related metabolites are classified according to their biosynthe-
sis as phytoanticipins (constitutive production) and pathogenesis-induced phytoalex-
ins [141]. Plant phytoalexins and phytoanticipins comprise metabolites produced in various
Agronomy 2023, 13, 1822 10 of 23
metabolic pathways, including the shikimate pathway (phenylpropanoids), mevalonate

pathway (terpenes), the urea cycle (alkaloids, polyamines), carbohydrate metabolism, and
fatty acid metabolism [127].
4.2.1. Alkaloids
Plants produce a wide range of nitrogen-containing secondary metabolites with an-
timicrobial activity, called alkaloids [142]. Plants in the Solanaceae family produce tropane
alkaloids, pyrrolizidine alkaloids, and steroidal glycoalkaloids [143]. These compounds
protect against insects, herbivores, and pathogens. The two main and best-described potato
alkaloids are α-solanine and α-chaconine and they belong to the group of cholesterol-
derived steroidal glycoalkaloids. Tubers from wild potato species commonly contain these
glycoalkaloids at concentrations that exceed international health regulations for human con-
sumption [144], and melicopicine, solanidine, α-chaconine, and α-solanine were identified
as constitutive metabolites related to resistance to late blight [145,146] (Table 2). Interest-
ingly, several previous studies indicated that glycoalkaloid content per se is not the trait
correlated with resistance to late blight [144,147,148]. It seems that only the nonglycosy-
lated glycoalkaloid precursor solanidine is a potent inhibitor of P. infestans, indicating the
host-specific adaptation to potato glycoalkaloids [149]. The potential human toxicity of gly-
coalkaloids has led to guidelines that limit the glycoalkaloid content of new cultivars [150],
and a recent study claimed the lowest observed adverse effect level of daily glycoalkaloids
consumption at 1 mg per kg of body weight [151]. In summary, solanidine is a prospective
marker for genotypes with attenuated glycoalkaloid production, e.g., genotypes with a lim-
ited conversion of solanidine to solanine and a total alkaloid content within the safety limits.
A recent study showed that tropane alkaloid scopolamine inhibits sporangia germination
and viability, and that its application could promote the effects of a chemical pesticide [152].
This alkaloid is found in some members of Solanaceae, but given its infamous reputation, it
is unlikely that it would find a large-scale application in agriculture.
Table 2. Alkaloid inhibitors of P. infestans. NA, not available.
Class Name HMDB

α-Solanine HMDB0034202
Steroidal saponins
α-Chaconine HMDB0039353
Acridone alkaloids Melicopicine NA
Solanidines Solanidine HMDB0003236
Tropane alkaloid Scopolamine HMDB0003573
4.2.2. Phenylpropanoids
Phenylpropanoids represent a large class of secondary plant metabolites derived from
aromatic amino acids phenylalanine and tyrosine. It is estimated that variations of the
substituents on the benzene ring and the position of the propenyl double bond result in
more than 8000 different phenylpropanoid metabolites [153]. One of these compounds
is salicylic acid, a plant hormone well known for its role in plant defense mechanisms.
The salicylic-acid-deficient potato mutant showed a drastic increase in pathogen growth
that was correlated with compromised callose formation and reduced early defense gene
expression [154]. However, a higher level of salicylic acid is not correlated with resistance
to late blight [155]. Hydroxycinnamic acid and other phenolic acids exhibit antimicrobial
activity, and cell wall-bound phenolics contribute to cell wall strengthening and restrict
fungal penetration [156]. Many phenylpropanoid compounds are more abundant in re-
sistant genotypes or induced in response to P. infestans, and a recent study showed that
the phenylpropanoid pool composition could correlate with resistance [157]. Candidate
markers of resistance include coumarins, derivatives of hydroxycinnamic acid, flavonoids,
and quinic acid and derivatives (Table 3). The validity of these putative markers is yet to
Agronomy 2023, 13, 1822 11 of 23
be tested, but at least some of these compounds show the inhibition of pathogen growth at
physiological concentrations [158].
Table 3. Putative phenylpropanoid markers of late blight resistance. The listed compounds were
found in at least two of the referenced studies [47,138,145,146,157,159–164]. HMDB, The Human
Metabolome Database metabolite annotations.
Class Name HMDB

4-Coumaryl alcohol HMDB0003654
Coumarins Scopolin HMDB0303366
Scopoletin HMDB0034344
Catechols Paucine HMDB0029876
Flavonoids Rutin HMDB0003249
1-O-Feruloyl-β-D-glucose HMDB0302219
1-O-Sinapoyl-β-D-glucose HMDB0302379
Hydroxycinnamic acids and Caffeic acid 3-glucoside HMDB0303040
derivatives Ferulic acid HMDB0000954
N-cis-Feruloyltyramine HMDB0036381
Subaphylline HMDB0033463
5-O-Feruloylquinic acid HMDB0240478
p-Coumaroyl quinic acid HMDB0301709
Quinic acids and derivatives
Chlorogenic acid HMDB0003164
Quinic acid HMDB0003072
4.2.3. Terpenoids
Terpenoids are one of the largest groups of secondary plant metabolites, with diverse
functions in plant growth and development. Volatile terpenoids are involved in biotic
stress responses, and their role in repelling pests and attracting herbivore predators is
well known [165]. Antimicrobial activity has been reported for volatile and non-volatile
terpenoids, and late blight symptoms occur in parallel with a reduction in the expression
of a gene that encodes an enzyme that catalyzes the initial step of isoprenoid biosynthe-
sis [166]. An induced accumulation of different classes of terpenoids has been reported in
numerous plant-Phytophthora interactions [146,162,167,168], and the known isoprenoids
related to late blight resistance are phytuberin, rishitin, and its precursors lubimin and
solavetivone [169,170] (Table 4). These compounds inhibit Phytophthora growth but were
found to be ineffective when applied to leaf discs or used as protectant sprays [169]. The
reason could be toxicity, which is not limited to the pathogen. Plants actively detoxify
these phytoalexins through cytochrome P450 [171], and their natural occurrence occurs
predominantly in tubers. Putative terpenoid resistance markers suitable for MAS are re-
cently discovered steroidal saponins. Four compounds were identified in the leaves and
tubers of potato cultivars inoculated with P. infestans: neoindioside D, protoneodioscin,
barogenin-solatrioside, and barogenin-chacotrioside. All of these saponins showed a high
anti-oomycete activity with IC50 in the micromolar range [172].
4.2.4. Polyamines
Polyamines are aliphatic compounds that contain two or more amino groups with
a positive charge at physiological pH. Polyamine biosynthesis starts with arginine and
its conversion to polyamine precursor ornithine or agmatine [173]. The accumulation of
putrescine was reported in response to P. palmivora [174] and P. infestans [175]. However,
polyamines are ubiquitous molecules involved in various processes, such as growth and
development regulation, response to phytohormones, and abiotic stress [176–178]. Thus, it
is unlikely that polyamines could be suitable MAS candidates.
Agronomy 2023, 13, 1822 12 of 23
Table 4. Terpenoids that inhibit P. infestans. HMDB, The Human Metabolome Database metabolite
annotations; NA, annotations not available.
Class Name HMDB

Phytuberin HMDB0035754
Rishitin HMDB0035593
Sesquiterpenoids
Lubimin NA
Solavetivone HMDB0035657
Neoindioside D
Protoneodioscin
Saponins NA
Barogenin-solatrioside
Barogenin-chacotrioside
4.2.5. Lipidome
Lipidome has a critical role in plant biotic interaction [179]. Free fatty acid lev-
els increase with pathogen attack, affecting the composition and fluidity of lipids in
the plant membrane or the production of signals derived from fatty acids, including
oxylipins [180–182]. Early studies showed that oxylipins colneleic and colnelenic acid
accumulate more rapidly in a potato variety resistant to late blight and inhibit the growth
of mycelial P. infestans [183]. However, a later study did not find any correlation between
P. infestans resistance levels and oxylipin synthesis rates or concentration [184]. However,
oleic and linoleic acid (oxylipin precursors) were reported to be involved in the defense
against fungal, oomycete, and bacterial infections [167,185,186], and were suggested as
putative late blight resistance markers [146]. It has been proposed that oil bodies may
mediate defense against microbes, especially in senescent leaves [187]. This is in line with
the significant accumulation of triglycerides reported in the resistant wild potato genotype
S. pinnatisectum [138]. Lipids are also utilized as antibiofilm. The leaf surface of the resistant
genotype S. bulbocastanum is covered with heptadecenoyl-lysophosphatidylcholine (LPC
17:1) that inhibits the germination of the P. infestans spore and mycelial growth in vitro [163].
This metabolite was not found on the leaf of S. tuberosum and could be a suitable candidate
for MAS.
4.2.6. Volatiles and Other Compounds of Interest

Plants continuously release volatile compounds that facilitate communication and
interaction with the environment. The amount of emitted volatiles significantly increases
in response to damage, and it is higher under attack by hemibiotrophic or necrotrophic
pathogens [188]. The emitted volatile compounds include derivatives of C6-aldehydes,
such as Z-3-hexenal, Z-3-hexenyl acetate, and (Z)-3-hexen-1-ol. Recently, pretreatment with
Z-3-hexenyl acetate was shown to delay the onset of P. infestans infection and inhibit the
intensity of the sporulation [189]. Therefore, these volatile compounds are both markers
of biotic stress and candidate MASs for the breeding of more resilient genotypes. An
additional candidate for MAS is cysteamine, which accumulates in the resistant wild potato
genotype [138]. This simple alkylthiol exhibits antimicrobial activity, and its precursor
cystamine inhibits P. infestans growth [190,191] (Table 5).
Table 5. Other compounds of interest that inhibit P. infestans. HMDB, The Human Metabolome
Database metabolite annotations; LM ID, LIPID Metabolites And Pathways Strategy identifier.
Class Name HMDB/LM ID

Heptadecenoyl-lysophosphatidylcholine
Glycerophospholipid LMGP01050002
(LPC 17:1)
Acetate ester Z-3-Hexenyl acetate HMDB0040215
Dialkyldisulfide Cystamine HMDB0250701
Alkylthiol Cysteamine HMDB0002991
Agronomy 2023, 13, 1822 13 of 23
4.3. Proteome and Peptide-Based Analyses

The successful introduction of protein/peptide markers into breeding processes has
been hindered by poor accessibility, low throughput, and the higher cost of standard pro-
teome analyses. However, novel techniques have significantly increased the detection limits
and processing power of state-of-the-art liquid chromatography-mass spectrometry analy-
ses, reaching deep proteome coverage and a rate of 100 samples per day [192]. In contrast
to transcriptomic studies, proteome analysis provides the correct image of the molecular
mechanisms underlying the phenotype, including post-translational modifications and
real protein abundances that are not easily predictable from transcriptomic data [193]. For
example, Ali et al. (2014) reported that only 50% of differentially abundant proteins showed
a correlation with gene expression data in S. tuberosum under the P. infestans attack [194].
Thus, quantitative proteomics can generate data that could be directly used for MAS.
4.3.1. Candidate Proteins for MAS

To defeat harmful pathogens, plants employ a complex cocktail of antimicrobial
proteins that could be exploited as markers for the early selection of resistant genotypes. The
first work that demonstrated that selective monitoring based on tryptic peptides could be a
promising technology for marker-assisted selection was published in 2016 [195]. Putative
markers identified for P. infestans resistance included two Kunitz-type protease inhibitors,
glucan exohydrolase, peroxidase, cystatin-type protease inhibitor, serine carboxypeptidase
III, and nonspecific lipid transfer protein (a member of cysteine-rich antimicrobial peptides).
Different proteomics studies targeting leaves, tubers, and secreted proteins in the apoplast
have extended the list of putative resistance markers. These studies have identified the
expected targets (R proteins, osmotins, peroxidases, protease inhibitors, and lipid transfer
proteins), as well as transcription factors and multiple defense-related proteins, including
glutathione S-transferases, endochitinase, glycosyltransferase, glucosidases, and heat shock
proteins 70 [138,194,196–204]. However, most of these candidates for MAS need to be
validated in dedicated mechanistic studies. A recent study showed that an accumulation
of Small G protein StRab5b reduced the lesions on infected potato leaves [205], but it
remains to be seen how this alteration impacts the yield and other economically important
traits. The most interesting part of the proteome resides in post-translational modifications.
However, it is also the least accessible, and there have been only limited attempts to identify
putative links between protein modifications and resistance to P. infestans. Two of these
exceptions have been protein SUMOylation and protein methylation [201,206], and a recent
report showed that the basis of resistance denoted by the avirulence gene Avr8 is in the
manipulation of SUMOylation via a deSUMOoylating isopeptidase DeSI2 [207].
4.3.2. Antimicrobial Peptides—Prospective Targets for Enhanced Resistance

Plant antimicrobial peptides are typical for their basic nature, cysteine-rich sequence,
and amphipathic design. Many are encoded by a single protein-coding gene, and the
resulting precursor proteins are later cleaved and post-translationally modified [208]. An-
timicrobial peptides are estimated to account for up to 3% of the Arabidopsis gene reper-
toire [209]. Plant antimicrobial peptides are usually classified according to their sequence
and structural similarity. Antifungal activity has been reported for thionins, defensins,
snakins, hevein-like peptides, knottin-type peptides, and α-hairpinins [210–212]. Typi-
cal potato peptides are snakins that have been shown to mediate protection against a
wide range of fungi, bacteria, and yeasts [213,214]. The effectiveness of these endogenous
S. tuberosum peptides against P. infestans is unclear, and further research is needed. How-
ever, foreign or synthetic antimicrobial peptides have been found to provide resistance
against P. infestans, including syringomycin E and syringopeptin 25A from Pseudomonas
syringae [205], Stellaria media hevein [215], and the synthetic peptide NoPv1 [216].
Agronomy 2023, 13, 1822 14 of 23
5. Conclusions and Future Perspectives

P. infestans is a reemerging potato pathogen that causes significant economic losses
worldwide. A considerable amount of work and time has been spent to develop viable late
blight management, but the prevailing potato cultivars are susceptible to the pathogen and
fully dependent on regular fungicide application. However, the fast-evolving P. infestans
has already gained resistance to some fungicides and seems to always be one step ahead
of us. Furthermore, the extensive application of fungicides destroys our environment
and is not sustainable. Some studies indicate that RNA interference and gene silencing
could be the future of protection against P. infestans (reviewed in [217]). It is a publicly
more acceptable approach than GMO, but the cost-effectiveness and stability under field
conditions remain a challenge [218]. To fight this pathogen, we need new tools that could
be found in biological control agents or antimicrobial peptides, or by searching the genome,
proteome, and metabolome of wild Solanum species. The available data indicate that the
dosage of the fungicide could be decreased by combining it with more environmentally
friendly substances. However, the identification of factors such as dosage, application
methods, compatibility with the given fungicide, and persistence in the field is needed.
We also need to improve our plant breeding techniques, which are very slow and need
assistance from molecular approaches. Marker-assisted selection can speed up the process,
but it is still limited by the relatively high costs of the analyses. The most time-efficient
screening would require analyses of samples from the first field experiment (Figure 5).
However, despite the available automatization and sample pooling, 10,000 samples still
represent a daunting and expensive task for ‘omics’ analyses. The problem is also due
to our limited knowledge of resistance mechanisms and their interaction with abiotic
factors. These interactions could be critical, as illustrated in the regulation of RWP-RK
transcription factors in soybean infected with P. sojae [219]. As illustrated in this review,
many compounds that accumulate in response to infection or are more abundant in resistant
genotypes are not directly responsible for the observed phenotype, and more research is
needed to identify optimal targets for MAS. Lastly, lifting the GMO restrictions imposed by
some governments would significantly broaden our horizons.
Author Contributions: Conceptualization, H.D. and M.Č.; formal analysis, H.D., M.Č., R.H., M.G.,
E.H., M.K. and B.B.; writing—original draft preparation, H.D., M.Č. and M.G.; writing—review and
editing, M.Č.; visualization, M.Č., H.D. and M.K.; supervision, M.Č.; funding acquisition, B.B. and
M.G. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the project NAZV QK1910045 “Identification of Metabolites
Correlating with Quantitative Resistance to Phytophthora infestans”, and the Ministry of Education,
Youth, and Sports of the Czech Republic (grant no. CZ.02.2.69/0.0/0.0/19_073/0016670) with
support from the European Regional Development Fund—Project “Internal Grant Schemes of Mendel
University in Brno”.
Data Availability Statement: Data are contained within the manuscript.
Acknowledgments: We thank Vladislav Klička (VESA Velhartice) and Jaroslava Domkářová (Potato
Research Institute) for valuable comments and discussion.
Conflicts of Interest: The authors declare no conflict of interest.
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agronomy

Agronomy 2023, 13, 1822. https://doi.org/10.3390/agronomy13071822 https://www.mdpi.com/journal/agronomy

Agronomy 2023, 13, 1822 2 of 23

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Agronomy 2023, 13, 1822

3.4. Resistant Cultivars

3.4.3. New Breeding Technologies for Potato Improvement

3.4.4. Somatic Hybridization

4.1. Genome-Based Analyses

4.2. Metabolome-Based Analyses

metabolic pathways, including the shikimate pathway (phenylpropanoids), mevalonate

Table 2. Alkaloid inhibitors of P. infestans. NA, not available.

Class Name HMDB

Class Name HMDB

Class Name HMDB

4.2.6. Volatiles and Other Compounds of Interest

Class Name HMDB/LM ID

4.3. Proteome and Peptide-Based Analyses

4.3.1. Candidate Proteins for MAS

4.3.2. Antimicrobial Peptides—Prospective Targets for Enhanced Resistance

5. Conclusions and Future Perspectives

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