You are on page 1of 7

Research in Microbiology 159 (2008) 74e80

In a world of microbes, where should microbiology stand?

1. Introduction winter) until sun expansion will finally destroy Earth itself.
Save the planet is not a slogan for microbes, since they
Microbes and their viruses have always dominated the bio- can adapt perfectly well to all human activities and the Earth
sphere and will continue to do so. However, this reality has would be perfectly fine with a microbial-only biosphere.
been recognized only recently, even by microbiologists. As As a consequence of their antiquity and continuous domi-
a consequence, the place of microbiology has not been cor- nance, microbes and their viruses have evolved and diversified
rectly estimated. In particular, the microbial world has for much more than macrobes (as exemplified by the variety of
a long time been largely ignored by evolutionists, who have microbial metabolisms) and are the most abundant living enti-
focused on macrobes (plants and animals). This has changed ties by several orders of magnitude [45]. If science were to
in recent decades, thanks to the application of methodological reflect reality in the absence of any human prejudice, 99%
and conceptual advances from molecular biology to microbiol- of biology would thus be microbiology, whereas plants and
ogy. The universal tree of life turns out to be overpopulated by animals would be principally considered as a strange (albeit
microbes and engulfed in an ocean of microbial viruses. We very interesting) epiphenomenon. Of course, being macrobes
have thus experienced an ongoing revolution in our vision of ourselves, and science being a human activity, things do not
the biosphere and its evolution, which is not yet fully appreci- work that way. For a long time, our vision of the living world
ated. Old anthropomorphic prejudices and misleading termi- was restricted to the animal/plant dichotomy, and microbes,
nologies still resist and prevent us from fully realizing the once discovered, were first considered themselves as curiosi-
potential of this new vision. At the onset of a new century, ties. Annoying curiosities for sure, once it became apparent
120 years after the opening of the first Institute originally that some of these little creatures were responsible for major
entirely devoted to microbie (and 120 years after the crea- plagues throughout human history and are still ready to kill
tion of its first journal), it is a good time to rethink the place us in every corner of a hospital.
of microbiology in the life sciences and to face its bright future
with optimism. 2. Microbiology and molecular biology: a complex
Life probably appeared on our planet sometime between love affair
the end of the late heavy bombardment (e.g. 3.9 Gy ago)
and the oldest known bona fide microfossils (2.7 Gy) [15]. Microbiology (formerly microbie), as a new quarter in biol-
For the first two to three billion years, life was only microbial, ogy, started brilliantly in the nineteenth century, when Pasteur
since macrobes (large animals, fungi and plants visible to the and a number of other great scientists identified several mi-
naked eye) only appeared 600 million years ago. Microbes crobes at the origin of important life-threatening diseases
(archaea, bacteria, unicellular eukaryotes) and viruses infect- and major natural processes useful for our well-being
ing them, still dominate the present biosphere. On one hand, (making wine, for instance). However, for a long time, our an-
microbial organisms are far more numerous than macrobial thropocentric view of the world prevented us from fully
ones by several orders of magnitude. On the other, plants realizing what was going on. When I first had a lecture on bac-
thrive thanks to their association with endosymbiotic cyano- teria in 1969 at the University of Paris 7, it was taught in the
bacteria (chloroplasts) and all eukaryotic macrobes rely on course of botany! Because they had cell walls, bacteria were
the original symbiosis of one of their ancestors with an a- considered tiny plants, and biology was still dominated by
proteobacterium (the progenitor of mitochondria). The origin the old macrobial dichotomy (zoology versus botany). Two
of macrobes themselves can probably be linked to the large years later, in the new course of molecular biology, I finally
rise in oxygen in the atmosphere triggered by microbial life, learnt that bacteria are not plants after all, but prokaryo-
and macrobes today are the hosts of large microbial communi- tesdthe ancestors of eukaryotes [38,39]. The newly designed
ties that are essential for their survival (there are more bacteria eukaryote/prokaryote dichotomy based on cellular structure
than human cells in our body). Finally, microbial life will sur- became the modern and fashionable view (compared to the
vive all catastrophic events that may possibly jeopardize the five kingdoms of Whittaker and previous classifications that
fate of our planet (from meteorite bombardment to nuclear were based on the structure of organisms) [46]. We were

0923-2508/$ - see front matter 2007 Elsevier Masson SAS. All rights reserved.
P. Forterre / Research in Microbiology 159 (2008) 74e80 75

finally more closely related to plants than plants were to bac- text imprinted in proteins, RNA and eventually DNA, and to
teria, and prokaryotes (bacteria and cyanobacteria) now occu- the visionary insight of Pauling and Zuckerkandl, who realized
pied half of the classification landscape (instead of one fifth in that the genetic text is a record of evolutionary history [50].
the Whittaker scheme). This was a revolution in our concep- Pasteur and Darwin thus finally met 30 years ago when Carl
tion of the world that emerged right away at the turn of the Woese and his colleagues of the Urbana school, using the
last century from the new concepts in cellular and molecular Sanger strategy to characterize 16S rRNA molecules, pub-
biology [38,39]. These new concepts themselves owed a lished in the November 1977 issue of PNAS their analyses
profound debt to microbiology, since the study of microbesd of rRNA oligonucleotide catalogues that surprisingly chal-
especially fungi, bacteria and their virusesdas model systems lenged the prokaryote/eukaryote dichotomy. They found that
paved the way for the emergence of molecular biology. This some prokaryotesdthe methanogenic bacteriadare no
could have led to a re-evaluation of the status of microbiology more related to other bacteria than they are to eukaryotes,
as a (the) major discipline in biology. However, for many of challenging the idea that all bacteria belong to a single line
the early leaders in molecular biology, the study of microbes of descent [47]. The reconstruction of a universal tree based
was only a first obligatory step before jumping to more serious on 16/18S rRNA finally revealed the reality behind the sur-
tasks, such as the understanding of brain functions or cancer face, with macrobes representing only the tips of two tiny
development (something obviously critical for macrobes of branches (one for plants, one for animals and fungi) at the
our kind). As a consequence, microbiology was often un- top of the eukaryotic bush, itself comprising only one-third
officially but forcefully considered as a second-rate science, of global cellular biodiversity (see Fig. 1 in the paper by
mainly interesting from an applied perspective (microbes be- Lopez-Garcia and Moreira in this issue [26]).
ing tools for biotechnology or as agents of infectious diseases). Archaea turned out to be a gold mine for microbiologists
The situation could have been even worse, since it was even at and molecular biologists alike. The elaboration of the archaeal
one point considered that microbes were not a threat anymore concept is directly linked to the discovery of hyperthermo-
(for instance when the US Surgeon General William H Stewart philes and, together with the PCR gold rush, it triggered
announced in 1969 that its time to close the book of infec- a hunt for extremophiles that led us to re-evaluate the limits
tious diseases, the war against pestilence is over [41]. of Earth habitability [40]. Further work on Archaea revealed
For a long time, microbiology was thus not taught as a dis- more surprises; not only are these prokaryotes strikingly
cipline of its own at most universities and was still a minor different from the Escherichia coli standard model system,
component of biological departments around the world (with but, upon closer inspection at the molecular level, they are
few exceptions, such as, of course, the Institut Pasteur). In much more similar to us (eukaryotes) than they are to bacteria
particular, microbiology was nearly completely forgotten by [29]. This has already led to several major discoveries that are
evolutionists (and vice-versa, evolution was sidelined by mi- relevant for our own biology. For instance, the search for the
crobiologists). Considering that, according to the famous aph- archaeal type II DNA topoisomerase led, unexpectedly, to
orism of Theodosius Dobzhansky, nothing in Biology makes the discovery of the protein that triggers meiotic recombina-
sense, except in the light of evolution [9], one could have tion in eukaryotes [2]. For a very recent example, two papers
concluded at that time that Nothing makes sense in microbi- in Science report, in August 2007, the resolution of complexes
ology. However, this was not realized by most leaders of the between replication origins and the archaeal replication initia-
molecular biology revolution, because the concept of proka- tor, shedding light on the highly similar mechanism of the eu-
ryotes apparently makes some sense in the evolutionary land- karyotic origin of replication complex (ORC) [10,20]. Besides
scape by claiming that bacteria, with their primitive nucleus the archaeal saga, 16S rRNA comparison had many other con-
(this is what prokaryote means), preceded eukaryotes (with sequences for our view of early evolution. An early significant
their true nucleus) and were most likely monophyletic [39]. observation was that mycoplasmas are not primitive bacteria
This suggested that the last common ancestor of all living or- after all, but former Gram-positive bacteria that lost their
ganisms was a small primitive bacterium lacking a cell wall, cell wall in the distant past [49]. Evolution thus can go from
very similar to a Mycoplasma [44]. Although fashionable at complex to simple, even for microbes. The recently discovered
that time (as was the prokaryote concept itself), this view genus Nanoarchaea is very likely another example of such
was clearly biased by anthropocentric prejudices that evolu- a reductive evolution [5]. Could it be that both archaea and
tion goes from simple to complex (i.e. from bacteria to hu- bacteria evolved by reduction from a more complex microbial
mans) and that bacteria are all the same just because they ancestor (more akin to eukaryotic microbes) [16,34]? This is
are so different from usdeukaryotes (somewhat reminiscent indeed suggested by a recent comparative proteomic analysis
of racial prejudice!). It is significant that biologists were for [24].
a long time reluctant to consider as bacteria groups such as cy- The diversity of microbial phenotypes, including unusual
anobacteria or streptomycetes that did not fit with the view of morphological features, is now finally recognized. In particu-
bacterial morphology as either unicellular bacilli or cocci. lar, the discovery of bacterial groups with intracellular mem-
Fortunately, repaying its debt to microbes, molecular biol- branes (Planctomycetales, Poribacteria) including a nuclear
ogy finally exerted a critical impact on the development of envelope (Gemmata obscuriglobus) has even more strongly
microbiology, thanks to the pioneering work of Sanger and challenged the prokaryote/eukaryote terminology [18]. Is it
colleagues, who designed efficient tools to read the genetic politically correct for us to consider that we have the true
76 P. Forterre / Research in Microbiology 159 (2008) 74e80

nucleus after all, and that the nucleus of Gemmata is false (or complete the catalogue of complete genomes to cover all divi-
primitive)? For a fascinating story involving unusual bacteria sions, phyla, subphyla, etc. detected by environmental rRNA
that experienced tremendous morphological changes, I recom- sequencing, if we hope to truly understand the evolution of
mend the paper by Rosati and co-workers on the epixenosome microbes (i.e. 99% of life). The availability of a robust species
(a bacterial ectosymbiont of a eukaryotic microbe): your con- tree is indeed a prerequisite to analyzing the evolution of all
cept of a bacterium will never be the same [32]. metabolic pathways and molecular structures that appeared in
The 16S/18S rRNA has been for the last thirty years the the course of cellular evolution and shaped modern organisms.
Rosetta stone of microbial evolution and the main descriptor
of biodiversity. The spectacular rise of molecular microbial 3. The viral ocean, a new playground for microbiologists
ecology, as a byproduct of the PCR revolution, has further
enlarged the microbial world to unexpected borders (see the A final touch to this picture was added when it was realized
chapter by Lopez-Garcia and Moreira in this issue [26]). Not that not only is the universal tree dominated by microbes, but
only do microbes dominate the universal rRNA tree of organ- also that this tree itself is immersed in an ocean of microbial
isms that we have been able to grow in the laboratory, but this viruses (viruses infecting microbes) [1]. Ecological studies
tree is itself a pale reflection of a much larger tree of rRNA focusing on viruses started to accumulate 20 years ago and
including the microbes that we have not yet been able to showed that viruses are about 10 times more abundant than
cultivate [22]. The discovery of phylotypes corresponding to cells in marine environments [3,42]. This is probably true
new groups of Archaea, Bacteria and Eukarya dramatically il- for other environments as well, since all cellular organisms
lustrates what remains to be known of the microbial world can be the targets of multiple viruses. In agreement with these
(both in terms of quantity and quality). In particular, new assumptions, metagenomic analyses now reveal that viral
phyla of bacteria have been discovered at an amazing rate, genes are more abundant than cellular ones in the genosphere
with between 50 and 100 phyla now recognized (versus [11]. At the same time, structural studies of capsid proteins
around 10 in 1987 and 23 in the 2001 edition of Bergeys Man- and comparative viral genomics have shown that viruses are
ual) [12,19]. Some of these phyla are probably as diverse, and extremely ancient, since homologous features are shared by
exhibit the same level of evolutionary divergence, as Proteo- viruses infecting different cellular domains, suggesting that vi-
bacteria. More than half of them have currently no cultivated ruses were already there at the time of LUCA [1,14]. It is
representative. A few species of these new groups of Bacteria therefore logical to assume that viruses have always coexisted
and Archaea have been successfully put into culture these last with cellular organisms (probably ever since outnumbering
two years, leading to very important discoveries (such as the cellular organisms). If this is true, the overall bidirectional
major role of ammonium oxidizing archaea in the global nitro- gene flow between cells and viruses should have been quanti-
gen cycle) [23,25,26]. This is now leading to a re-evaluation of tatively in favor of transfers from viruses to cells. This logi-
the importance of cultivation, itself dependent on a profound cally implies that viruses have played a major role in
understanding of microbial physiology and of the involvement biological evolution, transferring molecular novelties, first in-
of microbes in geochemical cycles [26]. vented in the viral world, into the cellular world [14]. It seems
The general shape of the tree of life, with three distinct do- quite clear now, for instance, that bacteria acquire their arsenal
mains and the overwhelming dominance of microbes, has been of toxins and other pathogenicity factors mainly from inte-
validated by all comparative analyses performed since the be- grated viruses [6]. This has again been recently exemplified
ginning of the genomic era, and the existence of a huge hidden by similarities between the type VI secretion system of Vibrio
world of unknown microbes has been confirmed by the first cholerae and the tail-spike protein complex of the bacteriovirus
metagenomic analyses [12,26]. A big challenge now will be T4 [36]. Not only can viruses provide extra features of selec-
to sort out the phylogenetic relationships between the various tive advantage for cellular organisms, but they can introduce
phyla and/or divisions identified by 16/18S rRNA analyses dramatic changes in their basic fabric, as illustrated by the viral
inside each cellular domain. It has sometimes been argued origin of mitochondrial transcription and the replication appa-
that this is impossible because the history of species has ratus [13]. As a consequence, viruses have been introduced as
been blurred by extensive lateral gene transfers. However, in key players in several recent evolutionary scenarios, from the
the case of Archaea at least, phylogenetic analyses have dem- origin of DNA to the origin of the eukaryotic nucleus [7,14].
onstrated the existence of a core of genes whose phylogeny The recognition that viruses are major components of the bio-
retraces the history of the organisms [4]. It can be hoped sphere and should be taken into account in any evolutionary
that similar types of analyses will finally reveal deep branch- scenario has finally completed the Woesian revolution by uni-
ing topology in Bacteria and Eukarya as well. Comparative fying the living world into a single evolutionary picture.
analysis of gene content and careful polarization of indels
(insertionedeletion) in core genes (not affected by gene trans- 4. Whats in a name?
fers) could complement the use of traditional phylogenetic
analyses to test parts of the trees that are not well resolved, Microbiology, as the science of microbes and their viruses,
or to solve contradictions between different trees. All these obviously covers the most profound and relevant aspects of
strategies require the analysis of complete genome sequences, biology. As expected from what we know of human history
which means that it will be essential in the next few years to (the interplay of revolutions and counterrevolutions), this has
P. Forterre / Research in Microbiology 159 (2008) 74e80 77

not been fully realized by fellow macrobiologists and even by a bacterium and an archaeon ([27] and references therein). Re-
most of us (microbiologists). Misleading anthropocentric con- ciprocally, these scenarios are accepted partly because they fit
ceptions and old terminologies continue to be pervasive in bi- the old prejudice, although they require ad hoc (to me highly
ology. To start with a minor example, it is amazing that most unlikely) explanations for the origin of the many eukaryotic
bacteriologists and nearly all molecular biologists are still features lacking in Archaea and Bacteria (such as the spliceo-
happy to define their favorite bacterium as Gram-negative, some and nuclear pores) and, more generally, to explain the
even though this does not make sense, since 21 out of the transformation of two domains into a third one (for in depth
23 phyla of bacteria now recognized in Bergeys Manual are critical analysis of fusion scenarios, see Ref [33]). Second,
composed of Gram-negative bacteria [19]! More troublesome, in the genomic and post-genomic era, the eukaryote/prokary-
in many scientific papers and comments in prestigious jour- ote nomenclature fits well with recent trends favoring global
nals, molecular biologists and biochemists continue to speak approaches in biology that seem modern compared to the
of lower and higher eukaryotes, a notion that directly re- reductionism of the last decade. Although focusing exclusively
fer to the Scala natura of Aristotle! This is probably why on reductionist approaches has its own limitation, one should
the universal tree of life is still rooted in the bacterial branch not forget that this approach was essential to dig into the es-
in most textbooks, despite the absence of robust support [16], sence of organisms and to identify the structure of the univer-
simply because traits common to Archaea and Eukaryotes are sal tree by focusing on the ribosome. Global approaches
considered by definition to be higher features compared to performed without a critical view have the negative conse-
bacterial ones. We (eukaryotes) are indeed strange creatures, quence of maintaining the biologists focus on the superficial
with our incredible spliceosome machinery, nuclear pore gi- similarities that exist between the structure of the archaeal
gantic complex and other features whose origins remain mys- and bacterial genomes, without asking whether these features
terious, but this does not imply that these features have are primitive due to convergent evolution or if they correspond
evolved more recently than operons (making gene regulation to real synapomorphies (shared derived traits) between
so much easier) or bacterial DNA gyrases (such a fascinating Archaea and Bacteria. The term prokaryote misleads us again
enzyme that can couple the intracellular ATP/ADP ratio to the on that issue by suggesting that the question has been solved
activated state of DNA). Specific eukaryotic features could and that these traits are primitive in the first place. They might
also be primitive traits, remnants of evolutionary scenarios be, but we still have to get convincing evidences for it, which
that we simply cannot imagine at present. Unfortunately, the is presently not the case.
general acceptance of the prokaryote first concept still
biases most work on the nature of LUCA, the rooting of the 5. The pro and cons of model organisms
tree of life, and the origin of eukaryotic features.
The prokaryote/eukaryote terminology itself continues to There is more at work than nomenclature behind the resis-
be currently used and even strongly defended by some biolo- tances to an evolution-oriented view of the biosphere. Indeed,
gists (see the recent debate in Nature between Norman Pace, 30 years after the Woesian revolution, the vast majority of
who suggested abandoning this nomenclature, and his oppo- bacteriologists continue to work on a very small number of
nents [28,30]). In my opinion, the term prokaryote is indeed models belonging to only two phyla (Proteobacteria and
misleading since, for many biologists, it is still synonymous Firmicutes, Gram-negatives versus Gram-positives) among
with bacteria (as previously noticed by Norman Pace, a chapter the 50 or so bacterial phyla recognized today. Similarly,
on prokaryotic transcription in most textbooks will generally most eukaryote model organisms belong to only two of the
mean transcription in bacteria [30]). This situation is worsened eight major eukaryotic divisions, the Opistokonts (animals
by the continuous use of the term archaebacteria which and fungi) and the Viridiplantae (plant), with other divisions
fools people into thinking of Archaea as some kind of strange that only include microbes still being largely ignored. The sit-
bacteria [48]. As a consequence, bacterial traits are sometimes uation is slightly better with archaeal studies since, from the
wrongly attributed to Archaea as well, or Archaea are simply beginning, scientists working on Archaea (embracing the
ignored in prokaryotic molecular biology. A strange situa- Woesian revolution) have been more prone to appreciating
tion occurs in particular with archaeal viruses, which are often the biodiversity of this domain.
labeled as bacteriophages in textbooks and/or described The study of viruses also still suffers from our ancient
under the headline bacterial viruses just because any virus vision of the living world, even amplified by the fact that,
that infects a non-eukaryote is considered to be a bacterio- for most biologists today (except virologists!), viruses are
phage (this is one of the reasons I prefer to use here the only viewed as providing tool kits for genetic manipulations.
term bacteriovirus instead of bacteriophage). Although the situation is slowly improving (for instance,
Besides the force of habit and our natural preference for with a recent interest in cyanoviruses), most bacterioviruses
dichotomies, the eukaryote/prokaryote nomenclature still studied at the molecular level are still those infecting some
resists (and is even making a kind of comeback) for various genera of Proteobacteria and Firmicutes. We still have no
reasons which are interesting to list here. First, it is favored idea of the nature of viruses infecting the majority of archaeal,
by recent evolutionary scenarios that restore the traditional bacterial or eukaryotic phyla (or divisions). Head-and-tail
gradist view of evolution (prokaryotic firstdeukaryote after) bacteriophages (Caudavirales) are often assumed to repre-
by explaining the origin of eukaryotes via the association of sent all prokaryotic viruses, whereas human viruses are
78 P. Forterre / Research in Microbiology 159 (2008) 74e80

assumed to represent all eukaryotic viruses. The discovery of are historical entities that have been shaped by natural selec-
the amazing morphological diversity of viruses infecting a sin- tion and complex historical pathways which can only be un-
gle order of hyperthermophilic archaea (Sulfolobales) [35] and derstood via the prism of evolution.
the isolation of the giant Mimivirus [37] (with a genome two
times bigger than that of a Mycoplasma) clearly tell us that
more surprises are ahead for those who will meet the challenge 6. Future prospects
of searching for new viruses infecting poorly studied groups of
cellular organisms. Microbiology is on the rise. The number of papers dealing
The focus on model organisms has been essential for the with microbes and published in Nature and Science has in-
development of biology and will still be determinant in the creased these last few years, with emphasis on geo-microbiology
future, but this trend has to be balanced by an exhaustive and metagenomic studies. Alas, microbiology might finally
exploration of biodiversity (i.e. both by increasing the number benefit from media headlines once the actual prophecies about
and diversity of model organisms from an evolutionary per- the end of the antibiotic era and the emergence of new patho-
spective and by the systematic screening of everything out gens proves to be true. As stated recently by Julian Davies,
there). There is a risk that the current trend toward system Microbes have the last word, which is not surprising in
biology will again shift the pendulum towards models at a world dominated by microbes [8]. The growing threat of
the expense of diversity. On one hand, this could help to again pathogenic microbes will again shift microbiology towards
place some microbes on top of the biologists agenda (models the medical side, but will also force microbiologists to explore
will first have to be very simpledthus microbial), but on the new avenues. Dramatic advances have been made in our
other, this could again lead some biologists to forget the real knowledge of the mechanisms of pathogenicity, thanks again
living world. to molecular biology (see the chapter by Philippe Sansonetti
Surely it will take time for institutions and individuals to in this issue), but they still have to produce new treatments
shift their research programs in line with scientific break- in many cases. The rediscovery of phage therapy is a good
throughs, and the fact that most known human pathogens example of what should be done. Alongside many historical,
belong to Proteobacteria and Firmicutes is playing a role, physiological and practical reasons [21], phage therapy was
but the persistence of the old view of the microbial world partly forgotten because the diversity and dominance of bac-
among biologists is not only due to the weight of the past terioviruses has been largely underestimated. Now that envi-
or of medical microbiology, but likely to the failure of ronmental microbiologists have demonstrated that viruses
even new generations of microbiologists to fully grasp evolu- control the ecology of bacterial systems in the environment
tionary concepts. The teaching of microbiology has probably [42], it remains to be realized that the human body is also
had much to do with this situation, since the new concepts an environment for concluding that bacterioviruses are indeed
are only slowly replacing the old view in scientific programs. our best allies against pathogenic bacteria [43]. Considering
In particular, the study of evolution (not to mention microbial the human body as an environment (a very complex and inter-
evolution) has been absent in most biology curricula. I never esting one) should also help to join together environmental mi-
heard of Darwin during my studies in biochemistry, genetics crobiologists and medical microbiologists in the search for
or molecular biology at the University of Paris in the early unknown pathogens among the plethora of not yet cultivable
1970s and I suspect that this is still the case in too many pla- organisms that live with us or could invade us (a notre insu,
ces. The impact that physicists had on the birth of molecular [17]). It might be that not only rare diseases in search of
biology probably played a role in this context by slowing a cause but also major new plagues (the obesity pandemic,
down the diffusion of new evolutionary concepts in biology, for instance) could be related to a microbial agent or to a com-
since students in physics and chemistry are usually even bination of microbial agents (commensal and pathogenic)
more ignorant of basic aspects of the Darwinian theory living in delicate equilibrium [17].
than students in biology. Since physicists will probably However, although focusing primarily on applied microbi-
play an increasing role in the development of biology in ology is rational in anthropocentric terms, scientists and
this century by bringing new concepts and methodology, decision-makers in science should be aware that anthropocen-
the risk exists that these positive trends will be accompanied tric approaches can be misleading over the long term in sci-
by a negative one, a continuous underestimation of the im- ence programs (the Earth is not flat after all). Research
portance of evolution in biology. This pleads for the intro- programs driven by pure curiosity and our desire to finally un-
duction of Darwinism in the program of physics and derstand the world in which we are living as it is (and not as
chemistry. Ironically, the new surge of creationist theories we think it is) should be the major incentives in microbiology,
could have a positive impact by forcing biochemists, geneti- as in all other scientific disciplines. If this is understood, we
cists and microbiologists to think more about evolution [31]. will be able to face with optimism the bright future of micro-
Many of them still consider living organisms as machines (or biology. The vast reservoir of new molecular mechanisms,
systems) to be deciphered by logical thinking. It should be new metabolisms and/or fascinating new structures hidden in
realized that such mechanistic views could pave the way the microbial world is enormous, and will reward future gen-
for Intelligent Design (searching for the intelligent engi- erations of microbiologists with great discoveries. We can only
neer), and that living organisms and all structures therein hope that microbiology will in the end finally be recognized,
P. Forterre / Research in Microbiology 159 (2008) 74e80 79

and will occupy the place it rightfully deserves in a world of [17] Frank, D.N., St Amand, A.L., Feldman, R.A., Boedeker, E.C.,
microbes. Harpaz, N., Pace, N.R. (2007) Molecular-phylogenetic characterization
of microbial community imbalances in human inflammatory bowel
diseases. Proc. Natl. Acad. Sci. U.S.A. 104, 13780e13785.
[18] Fuerst, J.A. (2005) Intracellular compartmentation in Planctomycetes.
Acknowledgments and apologies
Annu. Rev. Microbiol. 59, 299e328.
[19] Garrity, G.M., Holt, J.G. (2001) The road map to the manual. In:
I am grateful to Claudine Elmerich for the invitation to G.M. Garrity, D.R. Boone, & R.W. Castenholz (Eds.), (2nd ed.) Bergeys
write this paper and to David Prangishvili and Simonetta Gri- Manual of Systematic Bacteriology vol. 11 (pp. 119e166) New York:
baldo for critical reading of several versions of the manuscript. Springer.
[20] Gaudier, M., Schuwirth, B.S., Westcott, S.L., Wigley, D.B. (2007)
This is a very personal view of the place of microbiology in
Structural basis of DNA replication origin recognition by an ORC
science, and I had to omit some very important aspects of protein. Science 317, 1213e1216.
this discipline for no good reason (for instance, all modern [21] Hausler, T. (2006) Viruses vs superbugs. A solution to the antibiotic
studies dealing with the location of microbes in space instead crisis? London: Macmillan.
of timed biogeographydor in a communityd biofilms). I [22] Hugenholtz, P., Pitulle, C., Hershberger, K.L., Pace, N.R. (1998) Novel
division level bacterial diversity in a Yellowstone hot spring. J. Bacteriol.
also apologize for a highly biased selection of references
180, 366e376.
and probably some important omissions. [23] Konneke, M., Bernhard, A.E., de la Torre, J.R., Walker, C.B.,
Waterbury, J.B., Stahl, D.A. (2005) Isolation of an autotrophic ammo-
nia-oxidizing marine archaeon. Nature 437, 543e546.
References [24] Kurland, C.G., Canback, B., Berg, O.G. (2007) The origins of modern
proteomes. Biochimie 89, 1454e1463.
[1] Bamford, D.H., Grimes, J.M., Stuart, D.I. (2005) What does structure tell [25] Leininger, S., Urich, T., Schloter, M., Schwark, L., Qi, J., Nicol, G.W.,
us about virus evolution? Curr. Opin. Struct. Biol. 15, 655e663. Prosser, J.I., Schuster, S.C., Schleper, C. (2006) Archaea predominate
[2] Bergerat, A., De Massy, B., Gadelle, D., Varoutas, P.C., Nicolas, A., among ammonia-oxidizing prokaryotes in soils. Nature 442, 806e809.
Forterre, P. (1997) An atypical type II DNA topoisomerase from Archaea [26] Lopez-Garcia, P., Moreira, D. (2008) Tracking microbial biodiversity
with implication for meiotic recombination. Nature 386, 414e417. through molecular and genomic ecology. Res. Microbiol. 159, 67e73.
[3] Bergh, O., Brsheim, K.Y., Bratbak, G., Heldal, M. (1989) High [27] Lopez-Garcia, P., Moreira, D. (1999) Metabolic symbiosis at the origin
abundance of viruses found in aquatic environments. Nature 340, of Eukaryotes. Bioessays 29, 88e93.
467e468. [28] Martin, W., Koonin, E.V. (2006) A positive definition of prokaryotes.
[4] Brochier, C., Forterre, P., Gribaldo, S. (2005) An emerging phylogenetic Nature 442, 868.
core of Archaea: phylogenies of transcription and translation machineries [29] Olsen, G.J., Woese, C.R. (1996) Archaeal genomic: an overview. Cell 89,
converge following addition of new genome sequences. BMC Evol. Biol. 991e994.
5, 36. [30] Pace, N.R. (2006) Time for a change. Nature 441, 289.
[5] Brochier, C., Gribaldo, S., Zivanovic, Y., Confalonieri, F., Forterre, P. [31] Pallen, M.J., Matzke, N.J. (2006) From The Origin of Species to the
(2005) Nanoarchaea representative of a novel archaeal phylum or origin of bacterial flagella. Nat. Rev. Microbiol. 4, 784e790.
a fast evolving euryarchaeal lineage related to Thermococcales? Genome [32] Petroni, G., Spring, S., Schleifer, K.-H., Verni, F., Rosati, G. (2000)
Biol 6, R42. Defensive extrusive ectosymbionts of Euplotidium (Ciliophora) that
[6] Brussow, H. (2007) Bacteria between protists and phages: from antipre- contain microtubule-like structures are bacteria related to Verrucomicro-
dation strategies to the evolution of pathogenicity. Mol. Microbiol. 65, bia. Proc. Natl. Acad. Sci. U.S.A. 97, 1813e1817.
583e589. [33] Poole, A.M., Penny, D. (2007) Evaluating hypotheses for the origin of
[7] Claverie, J.M. (2006) Viruses take center stage in cellular evolution. eukaryotes. Bioessays 29, 74e84.
Genome Biol. 7(6), 110. [34] Poole, A., Jeffares, D., Penny, D. (1999) Early evolution: prokaryotes, the
[8] Davies, J. (2007) Microbes have the last word. A drastic re-evaluation of new kids on the block. Bioessays 21, 880e900.
antimicrobial treatment is needed to overcome the threat of antibiotic- [35] Prangishvili, D., Forterre, P., Garrett, R. (2006) Viruses of the Archaea:
resistant bacteria. EMBO J. 8, 616e621. a unifying view. Nat. Rev. Microbiol. 4, 837e848.
[9] Dobzhansky, T. (1964) Biology, molecular and organismic. Am. Zoolo- [36] Pukatzki, S., Ma, A.T., Revel, A.T., Sturtevant, D., Mekalanos, J.J.
gist 4, 443e452. (2007) Type VI secretion system translocates a phage tail spike-like
[10] Dueber, E.L., Corn, J.E., Bell, S.D., Berger, J.M. (2007) Replication protein into target cells where it cross-links actin. Proc. Natl. Acad.
origin recognition and deformation by a heterodimeric archaeal Orc1 Sci. U.S.A. 104, 15508e15513.
complex. Science 317, 1210e1213. [37] Raoult, D., Audic, S., Robert, C., Abergel, C., Renesto, P., Ogata, H., La
[11] Edwards, R.A., Rowher, F. (2005) Viral metagenomics. Nat. Rev. Scola, B., Suzan, M., Claverie, J.M. (2004) The 1.2-megabase genome
Microbiol. 3, 504e510. sequence of Mimivirus. Science 306, 1344e1350.
[12] Fierer, N., Breitbart, M., Nulton, J., Salamon, P., Lozupone, C., [38] Sapp, J. (2005) The prokaryote-eukaryote dichotomy: meanings and
Jones, R., Robeson, M., Edwards, R.A., Felts, B., Rayhawk, S., mythology. Microbiol. Mol. Biol. Rev. 69, 292e305.
Knight, R., Rohwer, F., Jackson, R.B. (2007) Metagenomic and [39] Stanier, R.Y., van Niel, C.B. (1962) The concept of a bacterium. Arch.
small-subunit rRNA analyses reveal the genetic diversity of bacteria, Microbiol. 42, 17e35.
archaea, fungi and viruses in soil. Appl. Environ. Microbiol. 73, [40] Stetter, K.O. (2006) History of discovery of the first hyperthermophiles.
7059e7066. Extremophiles 10, 357e362.
[13] Filee, J., Forterre, P. (2005) Viral proteins functioning in organelles: [41] Stewart, W. (1969) Quoted in General trends in infectious diseases.
a cryptic origin? Trends Microbiol. 13, 510e513.
[14] Forterre, P. (2006) The origin of viruses and their possible roles in major [42] Suttle, C.A. (2007) Marine viruses e major players in global ecosystem.
evolutionary transitions. Virus Res. 117, 5e16. Nat. Rev. Microbiol. 5, 801e812.
[15] Forterre, P., Gribaldo, S. The origin of modern terrestrial life, HFSP J. (in [43] Thiel, K. (2004) Old dogma, new tricks e 21st century phage therapy.
press). Nat. Biotechnol. 22, 31e36.
[16] Forterre, P., Philippe, H. (1999) Where is the root of the universal tree of [44] Wallace, D.C., Morowitz, H.J. (1973) Genome size and evolution.
life? Bioessays 21, 871e879. Chromosoma 40, 121e126.
80 P. Forterre / Research in Microbiology 159 (2008) 74e80

[45] Whitman, W.B., Coleman, D.C., Wiebe, W.J. (1998) Prokaryotes: the Patrick Forterre
unseen majority. Proc. Natl. Acad. Sci. U.S.A. 95, 6578e6583. Institut Pasteur, Batiment Fernbach,
[46] Whittaker, R.H. (1969) New concepts of kingdoms of organisms. Science
163, 150e160.
25 rue du Dr Roux, 75724 Paris Cedex 15, France
[47] Woese, C.R., Fox, G.E. (1977) Phylogenetic structure of the prokaryotic Univ Paris-Sud, Bat 409, CNRS UMR 8621,
domain: the primary kingdoms. Proc. Natl. Acad. Sci. U.S.A. 74, 91405 Orsay Cedex, France
5088e5090. E-mail address:
[48] Woese, C.R., Kandler, O., Wheelis, M.L. (1990) Towards a natural
systems of organisms: proposal for the domains Archaea, Bacteria, and
Eukarya. Proc. Natl. Acad. Sci. U.S.A. 87, 4576e4579.
30 November 2007
[49] Woese, C.R., Maniloff, J., Zablen, L.B. (1980) Phylogenetic analysis of
the mycoplasmas. Proc. Natl. Acad. Sci. U.S.A. 77, 494e498. Available online 14 December 2007
[50] Zuckerkandl, E., Pauling, L. (1965) Molecules as documents of evolu-
tionary history. J. Theor. Biol. 8, 357e366.