Genomes of the class Erysipelotrichia clarify the firmicute origin of the class Mollicutes.
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2013 J63(Pt 7):2727-41. doi: 10.1099/ijs.0.. Epub
2013 Apr 19.Genomes of the class Erysipelotrichia clarify the firmicute origin of the class Mollicutes.1, , , .1Department of Microbiology and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, IL, USA. james2@illinois.eduAbstractThe tree of life is paramount for achieving an integrated understanding of microbial evolution and the relationships between physiology, genealogy and genomics. It provides the framework for interpreting environmental sequence data, whether applied to microbial ecology or to human health. However, there remain many instances where there is ambiguity in our understanding of the phylogeny of major lineages, and/or confounding nomenclature. Here we apply recent genomic sequence data to examine the evolutionary history of members of the classes Mollicutes (phylum Tenericutes) and Erysipelotrichia (phylum Firmicutes). Consistent with previous analyses, we find evidence of a specific relationship between them in molecular phylogenies and signatures of the 16S rRNA, 23S rRNA, ribosomal proteins and aminoacyl-tRNA synthetase proteins. Furthermore, by mapping functions over the phylogenetic tree we find that the erysipelotrichia lineages are involved in various stages of genomic reduction, having lost (often repeatedly) a variety of metabolic functions and the ability to form endospores. Although molecular phylogeny has driven numerous taxonomic revisions, we find it puzzling that the most recent taxonomic revision of the phyla Firmicutes and Tenericutes has further separated them into distinct phyla, rather than reflecting their common roots. PMID:
[PubMed - indexed for MEDLINE] PMCID: PMC3749518 The ribosomal phylogeny of the mollicutes and low G+C Gram-positive bacteria. Previously described groups are coloured (Weisburg et al., 1989). Members of the class Erysipelotrichia are shown in blue, the anaeroplasma group is shown in orange, the asteroleplasma group is shown in teal, the spiroplasma group is shown in purple, the Mycoplasma hominis group is shown in green and the Mycoplasma pneumoniae group is shown in red. Other low G+C Gram-positives are shown in grey. A wedge depicts taxonomic groups that have been collapsed. The top and bottom of the wedge describes the longest and shortest branch lengths found in each group. The total number of taxa is shown in parentheses. The root position for each tree is arbitrary. All trees are maximum-likelihood. Bootstrap values are for 1000 replicates. Bars, 0.5 substitutions per position. Fully expanded trees are shown in Fig. S2.Int J Syst Evol Microbiol. 2013 J63(Pt 7):.The frequency of gaps occurring at positions in the 16S rRNA gene sequence. 16S alignments were made for a) the class Clostridia (82 individual species), b) the class Bacilli (76 individual species), c) the class Erysipelotrichia (26 organisms with more than one strain of a species) and d) the phylum Tenericutes (56 organisms with more than one strain of a species). Each block in the diagram represents a nucleotide position and colouring is as follows: grey, a gap occurring at a frequency of less than 0.001; violet, a gap occurring at a frequency of less than 0.05; blue, a gap occurring a frequency of less than 0.2; green, a gap occurring at a frequency of less than 0.35; yellow, a gap occurring at a frequency of less than 0.5; orange, a gap occurring at a frequency of less than 0.75; and red, a gap occurring at a frequency of greater than 0.75. Variable regions V1–V9 are indicated for reference (B?ttger, 1996).Int J Syst Evol Microbiol. 2013 J63(Pt 7):.Characteristics of the genomes of members of the classes Erysipelotrichia and Mollicutes. The 23S rRNA gene tree from Fig. 1(b) is shown. For each genome, the first three columns of data show the number of protein-encoding genes, the mean DNA G+C content for all protein-encoding genes, and the percentage of genes in the genome that match the modal codon usage of any mollicute genome. In each case, collapsed taxa are depicted as a range. The remaining columns indicate whether the given genome has known genes for: purine biosynthesis (Pur, red), pyrimidine biosynthesis (Pyr, orange), fatty acid biosynthesis (Fab, yellow), arginine biosynthesis (Arg, green), tryptophan biosynthesis (Trp, blue) and the formation of endospores (Spo, purple). Presumed pathway losses are indicated by correspondingly coloured vertical bars on the branches in the tree.Int J Syst Evol Microbiol. 2013 J63(Pt 7):.Publication TypesMeSH TermsSubstancesFull Text SourcesMiscellaneous
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Harald Br&ssow*DOI:&10.20.12693
Environmental MicrobiologyThematic Issue on Pseudomonas pages 10&15, Author InformationNutrition and Health Research, Nestl& Research Center, Lausanne, Switzerland*For correspondence. E-mail ; Tel. +41 21 785 8676; Fax +41 21 785 8544.Publication HistoryIssue published online: 29 JAN 2015Article first published online: 17 DEC 2014Manuscript Accepted: 24 OCT 2014Manuscript Received: 21 OCT 2014
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Biology has been driven by the human desire for self-knowledge. The discovery of our intimate symbiosis with microbes raises the question about our identity. A central issue is whether the microbiome associated with humans changes our phenotype in an observable way. As we deal with a great multitude of colonizing microbes and as even monozygotic twins differ substantially for their microbiome, we might deal with a dynamic system that is highly sensitive to initial conditions for which long-term prediction are impossible according to chaos theory. The overall colonization of the human alimentary tract can be teleological rationalized by a strong antimicrobial activity in the proximal and a mutualistic but controlled relationship with the microbiome in the distal gut segments. Yet the association of a specific microbiome with physiological traits turned out to be complicated and became frequently only clear after microbiota transfer experiments into gnotobiotic mice as a reductionist approach. As pathogenic bacteria create human phenotypes by their presence, mutualistic bacteria create symptoms (phenotypes) by their absence as exemplified by lactobacilli in bacterial vaginosis.When the ancient Greeks had burning questions, they turned to their gods for an answer at oracles. The Oracle of Delphi was the most famous where a female priest of Apollo under the influence of inhalations uttered prophecies that were frequently enigmatic or equivocal. However, modern thought was also born in Delphi where the temple of Apollo also carried the inscription of a philosopher which read: &&G&ῶ&& &&&&&&&& (gnothi seauton, know thyself). Self-knowledge as the basis for all knowledge, a bit of wisdom and a good deal of technique. Another Greek philosopher took one for his time unusual approach to human self-knowledge by studying comparative animal anatomy and thus became the father of biology (Aristotle, ). By these systematic studies, Aristotle observed homologies between the body parts of animals and humans and later defined humans as a specialized animal (in his words a &&ῷ&& &&&&&&&&&&, zoon politikon, a political or social animal) (Aristotle, ). After these promising beginnings, biological research took nearly 2000 years of sleep before it woke up again in the 16th century. Interestingly, anatomical plates with human dissections from that period were frequently decorated by the words &Nosce te ipsum&, which are nothing else than the Latin translation of the Greek &know thyself&. The next breakthrough in our self-knowledge came when Carl Linneaus introduced humans (Homo) next to monkeys (Simia) under the common heading of Anthropomorpha in his book &Systema Naturae& (Linn&us, ). Proudly, he printed the &Nosce te ipsum& in the 1748 edition of his book as sole description of our species apart from mentioning the four human races. The next and indeed a giant step in human self-knowledge came when Charles Darwin linked humans to apes by evolutionary relationships in his books &The Origin of Species& (1859) and &The Descent of Man& (1871).Biology has flourished since Darwin's time. It is thus hard to decipher the next decisive steps in human self-perception from the viewpoint of biology. The Human Genome Project is probably the next milestone in the &know yourself& journey. The human nature is now written if not in stone then at least in silicon. Those able to read the four-letter alphabet of life can now decipher our secrets. Many passages of this text are still as obscure as the answers of the Oracle of Delphi, but some major conclusions were already drawn from this text. Not the least is the observation that our deoxyribonucleic acid (DNA) sequence is derived from apes and & viruses, referring to the many retrovirus elements in our genome.It appears that DNA sequencing machines have currently become our main source of knowledge in biology. After the Human Genome Project, we are deciphering the genomes of the microbes filling the biosphere and colonizing our body (Human Microbiome Project) (Ding and Schloss, ; Human Microbiome Project Consortium, ; Turnbaugh et&al., ). We had to realize that the bacteria inhabiting our intestine constitute 10 times more cells than are found in our body and 100 times more genes than are detected in our genome. That we are not alone was known for a while & latest since 1676 when the Dutch amateur scientist and founder of microbiology, Antoni van Leeuwenhoek, visualized bacteria scratched from his mouth under his early microscope. However, the extent and diversity of our colonization with these tiny clandestine passengers surpassed our expectations.Do we now have to rethink the &gnothi seauton& taking in account that we a super-organism consisting of a human body and its colonizing microbes? Are we at the threshold of a new picture of Man and Human Nature (Relman, )? An answer to this question depends on the nature of our relationship with these microbes. How intimate is this relationship? Do microbes determine or at least influence some of our phenotypes (Hanage, )? Do we depend on them for some properties? Or do we mostly sport a neutral relationship with commensals where many small effects compensate each other making a resultant effect and phenotype non-observable? In the following I cannot provide an answer, but & hopefully & some food for thought.As demonstrated by the Gordon group even monozygotic twins sharing an identical human genome suddenly differ substantially in their genetic constitution when including their Microbiome (Turnbaugh et&al., ). But do these twins differ in a relevant phenotype beyond the composition of the gut microbiome? In general not very much and where they differ to the eyes of a dedicated observer, one would be hesitant to attribute this to the colonizing microbiota. However, the very fact that monozygotic twins differ as much in bacterial colonization as dizygotic twins is a challenging observation. An ecological dictum says &Everything is everywhere, but the environment selects& (O'Malley, ). In monozygotic twins, the niche is as similar as it can be in biology, and they share in addition a similar environment leading to a roughly similar exposure to microbes. Still they differ substantially for the gut microbiota composition. This observation indicates a strong stochastic (non-deterministic, random) element in our relationship with microbes. Such relationships are notoriously difficult to study since they need application of chaos theory, which studies the behaviour of dynamic systems that are highly sensitive to initial conditions & a response popularly referred to as the butterfly effect initially developed for weather forecast (Lorenz, ). Small differences in initial conditions (in our case: what microbes are met first) yield widely diverging outcomes for such dynamical systems, rendering long-term prediction impossible in general. Already this observation tells us that the challenge to analyse the host&microbe super-organism is a big one.Do we profit from our microbial symbionts? (Xu and Gordon, ) The answer to this question depends a lot on the host species under investigation. A cow without its rumen microbiota would be unable to extract energy from its grass food. For ruminants, the relationship with the microbial world is thus a matter of life and death. In other cases, the microbial impact is less dramatic, but still consequential. Coprophageous animals like mice or the gorilla would develop vitamin deficiency or difficulties to digest leaves, respectively, if prevented from eating their feces. But what for humans if one imagines a bacteria-free human subject, impossible as it is in practical and ethical terms? Would this condition lead to an observable phenotype? Clinicians might suggest a vitamin deficiency as likely consequence or problems in the fine-tuning of metabolic regulation. Work with germ-free animals suggests that we have co-evolved with microbes to a degree that our developing immune system needs instruction from microbes for its maturation (Chung et&al., ). The same can be said about the morphological maturation of the intestine in the post-natal phase which is also substantially influenced by the gut microbiota (Tomas et&al., ). However, these arguments are slightly circular. We need this instruction of the developing immune system by microbes because a major function of the immune system is to later fight off microbes. In a theoretical germ-free world, this part of our immune system would become dispensable. The same argument could possibly be made for a gut where maturation is needed to control the microbial commensals (literally: eaters from our table).Already a superficial look into our alimentary tract will shed some light on our relationship with the microbial world. The design of the gut is an old biological invention which comes in many variations. Basically, it is an internalized part of the external world crossing our body to increase surfaces for absorbing nutrients. Here a few pertinent facts. Food is contaminated with microbes. Very early, humans invented cooking to increase the palatability of food and to decrease its microbial contamination (Boaretto et&al., ). During the Neolithic revolution humans also domesticated harmless bacteria (e.g. lactic acid bacteria) to ferment raw food into a better digestible and microbiologically safer product (Mira et&al., ). Evolution comes to help with an efficient chemical trap: the stomach. With its high acidity and high proteolytic enzyme content, it digests and sterilizes food before it enters the intestine. Hence microbial counts are small in the small intestine (Wilson, ), and the next chemical trap waits for microbes in the form of bile acids. This situation makes biological sense: into the upper part of the small intestine digestive enzymes are excreted and nutrients are absorbed. If bacteria were present in that part of the intestine, they would compete with the acquisition of nutrients by our body. The absorptive capacities of the gut decrease along its length, while bacterial counts increase. Teleologically, the picture is clear: the human physiology tells us that microbes in the upper part of the intestine are seen as enemies or at least undesired competitors for food, and they need to be kept at low level. Two further physiological observations add to this impression. As we need to process chemical energy constantly to keep our body alive, we must fill the gut regularly with food. Its transport is achieved by gut peristalsis to achieve a steady state. This propulsion towards the anus will also flush all intraluminal bacteria that happen to survive in the small intestine towards their elimination. Some bacteria have learned to escape peristalsis by adhering to the epithelial lining of the gut. Here, we see another potent defence system in action. The epithelial lining of the gut is rapidly shed (Cliffe et&al., ). After about a week, the entire gut epithelia are replaced by cells migrating from the crypts of the gut. In summary, in the small intestine bacteria are considered as foes, we try to keep them in check and we accept high metabolic costs for these control measures. If these controls fail, clinicians know the dire consequences. If bacteria colonize the stomach, ulcers are observed. If insufficient gastric acid is produced, you get vulnerable to diarrheal diseases (Martinsen et&al., ). In case of stasis of intestinal motility, bacterial numbers increase leading to bacterial overgrowth and malabsorption (van Citters and Lin, ). Some indirect evidence even links bacterial overgrowth with malnutrition in developing countries.In the large intestine, we find an opposite situation from the small intestine. Bacterial numbers are large and absorption capacities are limited. In the colon, we resorb essentially only water and short chain fatty acids (SCFA) (acetate, butyrate and propionate). The latter observation is interesting since it results from co-evolution with our colonizing bacteria. Our enzymatic endowment cannot digest plant fibres, while many gut bacteria, particularly Bacteroides (Sonnenburg et&al., ) and Bifidobacteria (Schell et&al., ), are well equipped with polysaccharide-digesting enzymes. Plant fibre thus pass the small intestine undigested and reach the large intestine where they become food for these specialized colon bacteria which excrete SCFA as metabolic end-product which our metabolism can again use. Their waste becomes thus our food. The epithelia of the colon are entirely fed by butyrate produced by colon bacteria. It was estimated that 5% to 10% of our daily caloric consumption comes from SCFA produced by colon bacteria. Recent data indicate that bacterially produced SCFA from the colon play a role beyond being energy carriers (Br&ssow and Parkinson, ). Acetate and propionate are important signalling molecules affecting glucose homeostasis via a gut&brain axis (De Vadder et&al., ). A gut&lung axis has also recently been defined using SCFA (Trompette et&al., ). When considering the colon, gut bacteria appear as co-evolved friends. Epidemiologists and microbiologists have clearly established the beneficial role of plant fibres in the human diet, and these effects are hardly rationalized without the metabolic activity of colon bacteria (David et&al., ). In summary, we see a clear double strategy in the gut: defence against bacteria in the upper parts and acceptance of bacteria in the lower parts. This does not mean contradiction but compromise. Since bacterial contamination of a gut is inevitable and control can only be maintained at a high energy cost, control is only executed where absolutely essential. However, we should not underestimate the degree of control in the large intestine. The fact that bacterial counts are high in the colon does not necessarily mean that they are uncontrolled. The gut-associated immune system elaborates many immune cells and leads to the secretion of a large amount of immunoglobulin A into the gut which outnumbers by far the amount of immunoglobulins produced into the circulation. Immunoglobulin A-deficient children show moderately increased rates for mucosal infection (Strugnell and Wijburg, ), and IgA-deficient mice show an altered composition of the colon microbiota with a dramatic increase in segmented filamentous bacteria (Suzuki et&al., ). It is thus safe to postulate that part of this intestinal immune activity serves to control the composition of the commensal bacterial populations colonizing the gut.Many conclusions about the beneficial effect of gut bacteria are derived from experiments with the laboratory mouse. For example, conventional mice showed a better growth than germ-free mice receiving the same amount of food calories (B&ckhed et&al., ). Clearly, gut bacteria contribute to energy extraction in mice. However, other experimental systems teach a different lesson. Germ-free chicken show in striking contrast a better growth than conventional chicken when on the same calorie supply (Coates et&al., ). Apparently, it depends on the animal species whether gut bacteria have an overall growth-promoting or growth-depressing effect. When you compare the evolution of different organ systems, you see different speeds of evolution. The liver is a slow evolver across the animal kingdoms, the cardiovascular system is pretty well preserve the alimentary system, in contrast, evolves in the fast lane. While we share gut and food preference with our closest primate relative, the chimpanzee, we find already a drastically different gut system in our next closest relative, the gorilla (a coprophageous leaf eater). It is thus risky to draw conclusions from a comparison of mice and men when it comes to gut physiology. Not surprisingly, we have a rather distinct gut microbiota from mice. Another controversy illustrates the difficulty to assess the role of gut bacteria in nutrition. Recent clinical observations suggest that re-feeding of malnourished children achieves better results when antibiotics are given concomitantly (Trehan et&al., ). This observation reminds the widely practice of adding antibiotics as growth promoters in animal rearing (Cromwell, ). The jury is still out with respect to the antibiotic effects in nutrition. Do they act via infection control, or do they suppress or modulate the gut microbiota leading to a better food use or do antibiotics affect directly the host cells? We do not yet know the answer to these questions which are of substantial societal importance.Let's go back to our initial question: are we at a new level of defining human nature as a human-microbe consortium? After reading these lines, you probably got a somewhat blurred impression. To answer this question positively, we would need clear phenotypes for a specific human&microbiome consortium. If one takes the intensively investigated question of the distinction of lean and obese human subjects, initial data linking it to disequilibria between Bacteroidetes and Firmicute-dominated gut microbiota (Ley et&al., ) were followed by conflicting reports (Duncan et&al., ) and then by the conclusion that the contribution of the microbiota to obesity-related metabolic phenotypes are unclear and likely multifaceted (Ridaura et&al., ). Interestingly, as in the case of malnutrition in children, microbiota transfers from human subjects showing a lean, obese or malnourished phenotype into germ-free mice frequently reproduced the phenotype in the experimental animal even if sometimes only under a specific abnormal diet (Ridaura et&al., ; Smith et&al., ). Is the genetically outbred nature of human subjects or their non-deterministic prior bacterial colonization an impediment to observe clearer correlations between microbiota composition and host phenotype? This might well be the reason for the described difficulty since germ-free mice are defined for both conditions. It might also explain why lead scientists in the field of human microbiota research use monozygotic twins in their studies. By comparing monozygotic twins who develop distinct phenotypes (kwashiorkor malnutrition versus normal nutritional state) for their gut microbiota, they eliminate at least the human genetic diversity from the equation without, however, controlling the prior bacterial colonization effect. The fact that after microbiota transfer experiments germ-free recipient mice show the phenotypes of the donors underlines, however, the importance of the microbiota for a phenotype.Other observations demonstrate that a human-microbiota consortium can have a clear phenotype. Take as an example a patient suffering from a Clostridium difficile infection. These are typical hospital infections occurring after a preceding antibiotic treatment, which upsets the resident gut microbiota, giving a toxin-producing C. difficile a growth advantage. The infection causes symptoms from diarrhoea to pseudomembraneous colitis or a toxic megacolon, the latter are pathognomic for this infection (Bartlett and Gerding, ). The patient shows now a new phenotype, which is immediately recognized by a clinician as typical for this human&C. difficile consortium. Treatment is by an antibiotic active against C. difficile or by transfer of processed stool from a healthy donor proving the involvement of both the pathogen and the gut microbiota in this phenotype (van Nood et&al., ). In fact, when considering pathogenic microbes, we have a large set of distinct clinical phenotypes which a human being can develop under microbial influence, many rather typical for the microbe (think cholera or shigellosis which both can be easily recognized clinically). Medical microbiologists consider these phenotypes as consequence of specific virulence genes in the pathogen which have specific deregulatory effects on the host physiology resulting in disease (Ogawa et&al., ; Charles and Ryan, ).Why do we lack examples of clear-cut phenotypes for non-pathogenic bacteria colonizing the human body? A simple answer is: because they lack virulence genes. Mutualistic bacteria do not act against the host as pathogens, but they cooperate with the host. They become so much part of the ecosystem &man and microbe& that we do not easily detect their role unless we analyse their contribution to the physiological situation in detail. But there is a problem: pathogens announce themselves by disease symptoms, while health has no symptoms and is in fact very difficult to define (Br&ssow, ). Painstaking analysis of different physiological situation is necessary to explore where microbes might contribute to the &healthy& physiological phenotype since a priori we do not know whether microbes play an important role in the phenotype under question. This is in contrast to the situation with an infectious disease where the implication of the pathogen is part of the definition of the disease. The research literature started with addressing the physiological role of the gut microbiota in phenotypes like obesity. This is of course a difficult start since both the microbe side is complex (because of the enormous diversity of the gut microbiota) and & in addition & the link between microbial metabolites and obesity is likely a very complicated chain of events which we only started to decipher. However, there is hope: as it is the presence of a pathogen that makes symptoms, we can anticipate that it is the absence of mutualistic bacteria that also makes symptoms. Now we can start again with symptoms describing health deteriorations (do not expect diseases) and correlate it with the absence of specific bacteria. This task is of course the searching of the literal needle in the hay stack if you deal with a complex microbiota as that of the gut. If you turn, however, to less complex human microbiota like the human vagina and you apply this criterion, you immediately get a phenotype linked to the loss of a candidate mutualistic microbe. The phenotype is bacterial vaginosis which is the consequence of the loss of vaginal lactobacilli, the dominant microbial colonizers of the vagina (Ma et&al., ). The metabolic end-product of lactobacilli is lactic acid, which creates the physiological acidic milieu that protects the vagina against ascending genito-urinary tract infections.Now, we are back to the initial philosophical question about microbes and the human nature. Lactobacilli are perhaps an alter ego of us (if you are a woman), other examples certainly exist and remain to be discovered. The question of microbes and the human nature transgresses a philosophical discussion. It becomes a practical biomedical challenge to reconstitute mutualistic microbes where we lost them to ameliorate the health of humans. As beneficial microbes can be used for re-colonization (probiotic bacteria) of specific body sites or can be stimulated by providing specific nutrients (prebiotics), the food industry might get in the future more tools at hand to ameliorate human health where the pharmaceutical industry has strived to alleviate the burden of human disease, more specifically in our context of infectious diseases by eliminating pathogens.Aristotle (1990a) History of animals. English translation. In Great Books of the Western World, Vol. 8. Adler, M.J., Fadiman, C., and Goetz, P.W. (eds). 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