Learn more about Firmicutes
Immunoprotective Effects of Probiotics in the Elderly
Tennille Marx, in Foods and Dietary Supplements in the Prevention and Treatment of Disease in Older Adults, 2015
35.3.2
Microbiota Alterations in the Elderly
Two major microbial phyla – Firmicutes and Bacteroidetes – represent 99% of the bacteria in the gut. Even when taking large individual variation into account, the levels of these two dominant bacterial divisions, are known to shift dramatically with aging. It has been shown that the Firmicutes to Bacteroidetes ratio decreases from approximately 10.9 in middle-aged adults to 0.6 in the elderly [3]. This dramatic shift is one of the few age-related changes to the gut microbiota that has been consistent in human observational trials, and some have suggested that it could possibly be a parameter in assessment of the health of the gut microbiota [28].
In addition to the changes in bacterial phyla, there are also vast, yet variable, changes within the lower levels of bacterial classifications (order, genus, and species) in the elderly. There are a few common findings, however, that have been reproducible in scientific studies. For example, a significant decrease in Bifidobacterium and Lactobacillus bacteria has commonly been reported with aging [29–32]. However, newer reports, using updated identification techniques, have indicated that Bifidobacterium levels in the elderly are similar to those in younger people [33]. It is commonly found, however, that the diversity of species within these genera is negatively impacted in the elderly. While four or five different Bifidobacterium may reside in adults, only one to three species may be found in the elderly [33]. Specifically, Bifidobacterium angulatum, bifidum, longum, and adolescentis have been found to be more predominant in the elderly [4]. Accordingly, Lactobacillus plantarum, paracasei, and reuteri species have been shown to be more prevalent in the elderly compared to healthy adults, who have higher levels of Lactobacillus acidophilus and helveticus[32]. Additionally, studies appear to agree that there are age-related increases in facultative anaerobes, such as Streptococci, Enterococci, and Enterobacteria[28,34].
The majority of the bacteria in the phylum Firmicutes fall into two main groups; the Clostridium coccoides group (also known as Clostridium cluster XIVa) and the Clostridium leptum group (also known as Clostridium cluster IV). Clostridium counts in general have been found to be significantly higher in the elderly; however, Clostridium clusters XIVa have been shown to be significantly reduced in the elderly [35]. The bacteria in Clostridium cluster XIVa play major roles in the fermentation of carbohydrates within the gut [28]. The major end products of this fermentation in the gut are short-chain fatty acids (SCFAs). Butyrate, one of the best-studied SCFAs, is the main source of nutrition for cells of the gut epithelium. Depletion of butyrate is associated with impairments in the gut barrier integrity. A decrease in Clostridium clusters XIVa bacteria can result in a decrease in intestinal fermentation, and, theoretically, fewer SCFAs, or “food,” for the intestinal epithelial cells. SCFAs have also demonstrated anti-inflammatory and immunomodulatory properties [28].
Despite these recognized changes, scientists believe that it is the age-related overall decrease of microbial diversity in gut bacteria that is most detrimental, rather than alterations in one specific species over another. The age-related changes in the composition of the microbiota have been shown to be highly individual, as well as diet and geographically influenced [7,28]. Additionally, variations in bacterial identification techniques and the presence of an estimated>1000 different species of gut microbiota have made it difficult to find consistent age-related changes in specific genera or species in the elderly’s microbiota composition [7]. Further understanding of these specific age-related changes of the microbiota, however, could open doors to finding specific, individualized disease treatments, and provide a strategy for the prevention of disease and for healthy aging.
The Pneumococcal Cell Wall
Nicolas Gisch1, ... Waldemar Vollmer2, in Streptococcus Pneumoniae, 2015
Basic PG Structure and Modifications
Pneumococci have a PG structure typical for Firmicutes, made of glycan chains of alternating N-acetylglucosamine (GlcNAc), N-acetylmuramic acid (MurNAc), and peptides linked to MurNAc. The peptides are synthesized as a pentapeptide with the sequence l-Ala–d-(γ)Glu–l-Lys–d-Ala–d-Ala. Most of the d-Glu residues become amidated by MurT/GatD at C(α) to d-Gln, but a few percent of d-Glu residues escape this modification and are found in the cell-wall PG [5,6] (Figure 8.1). The peptides may also be modified by MurM/MurN with an l-Ser–l-Ala or l-Ala–l-Ala dipeptide (“branch”) linked to the ε-amino group of the lysine stem residue [7]. Most strains have a small percentage of branched peptides in their PG, but these are abundant in certain lineages of β-lactam-resistant strains. Shortly after synthesis, the peptides are either utilized to form cross-links connecting adjacent glycan chains, or they are trimmed to remove the d-Ala residues at positions 4 and 5 by the dd-carboxypeptidase PBP3 (DacA) and the ld-carboxypeptidase LdcB (DacB). Peptide cross-linking by dd-transpeptidases (penicillin-binding proteins, PBPs) leads to dimeric tetra-pentapeptides or trimeric tetra-tetra-pentapeptides (with or without the dipeptide branch), and these are trimmed to corresponding tripeptide versions, the tetra-tripeptide and tetra-tetra-tripeptide. If present at all, tetramers or higher peptide oligomers are of very low abundance. Hence, the most abundant peptides in mature PG are tripeptide monomers, tetra-tripeptide dimers, and tetra-tetra-tripeptide trimers, which can have a d-Glu residue instead of d-Gln due to incomplete amidation, and which can carry one or more dipeptide branches that may form an interpeptide bridge in cross-links [5].
The N-acetylamino sugars in the glycan chains are also subject to modification reactions. Some of the GlcNAc residues are deacetylated to glucosamine (GlcN) by the PG deacetylase PgdA [8]. Many MurNAc residues become acetylated at C6-OH by the PG acetyltransferase Adr, which for unknown reasons is required to express high β-lactam resistance [9]. PG O-acetylation competes with the attachment of WTA and capsular polysaccharides by LCP phosphotransferases, which occurs at the same position of MurNAc [10,11]. All these modifications and substituents at the glycan chain contribute to the resistance of the cell to lysozyme, an antibacterial host enzyme with cleavage preference to unmodified PG glycan chains. Hence, these modifications are abundant in pathogenic bacteria that are able to resist lysozyme.
Bacterial Infections of Laboratory Mice
Charles B. Clifford, Kathleen R. Pritchett-Corning, in The Laboratory Mouse (Second Edition), 2012
Biology
Streptococci are members of the Lactobacillales order of the Firmicutes. Whereas staphylococci divide along multiple planes to produce clusters, streptococci divide along a single plane to produce chains. Most are oxidase-negative and catalase-negative, and primary differentiation is usually based on patterns of haemolysis when grown on blood agar: alpha-haemolysis is greenish, beta-haemolysis produces a clear zone, and gamma-‘haemolysis’ is the term applied for no observable haemolysis. Beta-haemolytic streptococci are usually subdivided into Lancefield groups A, B, C and G based on serotyping of the capsular polysaccharides.
Gastrointestinal Microbial Ecology with Perspectives on Health and Disease
Merritt G. Gillilland, ... Gary B. Huffnagle, in Physiology of the Gastrointestinal Tract (Fifth Edition), 2012
40.5
Colonization and Succession of the Human Gut Microbiome
At birth, the infant GIT is completely sterile.46 The Firmicutesand Bacteroidetes that come to dominate the adult GIT cannot grow readily outside of their human host.39 How then does the gut become colonized by the rich and diverse community that is found in adults? What are the effects of delivery methods, antibiotics, and diet on initial colonization and succession? These questions, which are critical for human health, rely on many of the ecological principles that have been studied by macrobial and microbial ecologists.
Ecology is the study of the interplay between organisms, their physical environment, and other organisms that share the physical environment with them. One of the key concepts in ecology is competition. Competition for food and space (resources) can occur within a species or between species and is the major driving force behind natural selection and evolution. If one of the competitors is weaker or not as adept at utilizing a resource it will die out or be excluded. Competitive exclusion is the end result of competition forcing an organism to be excluded from a habitat. In the case of gut microbes, this could be competition for the same nutrient, such as a carbon source. No two species will utilize the same resource with the same efficiency. Ultimately, one species will reach a higher population density and force the competitor out of that habitat. Resource partitioning or niche differentiation (a process of natural selection that will force competitors to use resources differently) is a way to avoid competition between species and allow for coexistence. The inhabitants of the GIT microbial community are adept at resource partitioning.
Another important ecological term is niche. An organism’s niche is not so much its physical placement within an ecosystem but its role in the ecosystem. No two species can ever occupy the same niche. When two species do occupy a niche, then competition will force one of the organisms out. Bacteria can have metabolic niches. Where and how bacteria get energy leads to the development of metabolic niches.39 Gut bacteria are involved in methane production, sulfate reduction, and carbohydrate fermentation, all of which are metabolic niches.39
Symbiosis is defined as the “living together” of two different organisms. Organisms can live with each other, on each other, or within each other. The member within the relationship that has the other organism living in it or on it is the host. The member that is living in or on the host is the symbiont. Symbiotic relationships have consequences too. If both members of the symbiotic union benefit from the relationship, it is termed mutualism. If one member benefits and the other is unaffected, it is called commensalism. The biomedical literature usually describes the members of the bacterial microbiome as commensals; however, we now understand much more about the complex relationship between humans and their microbiome, and this symbiosis is clearly mutualistic.12,13,40,50–53It has been suggested that because the health of humans is so intertwined with their microbiome (and vice versa), that we are a superorganism.30,31 For example, the microbiome contains within its genome metabolic pathways that humans do not possess but that are necessary for our survival.31 Much of the microbiome cannot thrive outside of the human host. Given the extent of co-dependence between host and symbiont it seems fair to consider the idea of superorganism. Pathogenic species can be considered “cheaters” that benefit from the existing microbial community and at the same time can negatively impact the fitness of the host and microbial community.39
Lastly, ecological succession is the process of changes in species structure within an ecological community. New habitats are first colonized by a pioneer species, which is termed autogenic succession. Pioneer species are able to withstand more extreme or less favorable living conditions. Their presence in the environment can change both biotic and abiotic components of that environment and over time new species that would not have normally been able to colonize that habitat can do so. If an existing habitat is perturbed (fire, flood, act of god, or antibiotics in the case of microbes), the succession that follows is called allogenic. Succession will be an important concept for understanding colonization of the gut by microbes. The indigenous microbiota that have taken up residence within our GIT is called autochthonous. Microbes that are not part of our resident microbiome and are transient in nature are called allochthonous. The allochthonous members may come from diet, water, or from other sources in our environment.39
A better understanding of how the bacterial community forms (pioneering species), how community membership naturally changes over time (succession), and functional redundancy (resource partitioning) will be critical for understanding the role of the microbiome in health and disease. The human GIT is first colonized by facultative anaerobes such as Escherichia coli and Enterococcus spp.54 These early colonizers or “pioneers” are essential for transforming the environment into one that can be successfully colonized by other species. The early neonate GIT is not suitable for colonization by the majority of the microbes that will come to inhabit that ecosystem. The pioneering facultative anaerobes consume oxygen, produce carbon dioxide, alter the pH, provide additional sites for adhesion, produce nutrients, and lower the redox potential, which makes the environment suitable for strict anaerobes that will come to dominate the microbial community.43,54,55 By the first two weeks of life obligate anaerobes begin to appear (Bacteroides spp. and Bifidobacteriaspp.).56,57
The maternally derived pioneering species, and those species that follow, are very important in shaping the microbial community of the GIT. However, there are many other factors, besides microbial inheritance, that shape the community. Selection pressures on the host and the chemical and physical environment play crucial roles in community formation.39Natural selection, acting on the host, impacts microbial community membership and structure. This form of selection is called “top-down” selection and favors stability and functional redundancy.39
Research suggests that the neonate gut microbial community is inherited from contact with the feces and vagina of their mothers as well as the immediate environment.58,59 It was widely assumed that the first bacteria to colonize the neonate gut arose from the maternal vagina.57 However, it seems that during early neonate ontogeny the bacteria that are most successful at colonizing the human gut come from contact with the maternal fecal microbiota.57 However, the microbial community of the infant and adult GIT are different. The adult microbial community is more stable, while the developing infant microbial community fluctuates temporally (Figure 40.3).60Figure 40.3illustrates within-individual fluctuations of certain taxonomic groups and the differences in abundance between individuals. In nearly all cases the early microbial community was shown to be dominated by γ-proteobacteria.60 By 36 weeks of life, infants born vaginally, begin to have a microbial community that resembles the adult gut,56 and by approximately 2 years of age the adult microbial community is established.61 Ontogenetic change in community stability and structure is attributed to the incorporation of solid foods in the diet.56,60 Infants born via caesarian have an altered GIT colonization compared to those born vaginally.58 Interestingly, it may require up to 6 months for the microbiota to resemble those of infants born vaginally.58
Functional redundancy is the “ability of one microbial taxon to carry out a process at the same rate as another under the same environmental conditions.”62 Within the gut microbial community there are functional groups (guilds) of Bacteria and Archaea; that is, there are many species of Bacteria and Archaea that can perform the same function, such as fermentation, methane production, and sulfate reduction. Functional redundancy is what drives resource partitioning in the microbial community. If microbes can coexist by “sharing” resources this can alleviate or reduce competition. As stated earlier, competitive exclusion is a result of competition. If two species occupy the same niche then competition for that resource can drive one species to local extinction. Functional redundancy and resource partitioning can increase the stability of the gut microbial community by making it more diverse. The more diverse the ecosystem the more likely it is to withstand perturbations and repel invaders.63,64 A diverse and robust GIT microbial community can prevent pathogens from colonizing.65 Selection pressures on the microbe via the host and microbe–microbe interactions is called “bottom-up” selection, and this tends to drive microbes to become functionally specialized to avoid competition.39
The microbial community of the gut occupies three major metabolic niches: (1) fermentation, (2) sulfate reduction, and (3) methanogenesis. The majority of species, belonging to the phyla Firmicutes and Bacteroidetes, are involved in fermentation. Undigested carbohydrates (resistant starches and plant polysaccharides and oligosaccharides) constitute the majority of food available for fermenting bacteria.66 Two bacterial genera (Desulfovibrio spp. and Desulfotomata spp.) have been identified as sulfate reducers. The archaeal members that have been shown to produce methane are Methanobrevibacter smithii and Methanosphaera stadmaniae. Only members of Archaea have been shown to produce methane. Bacteria involved in fermentation dominate the GIT microbial community, because the vast majority of available nutrients are derived from host-ingested carbohydrates. Understanding the dynamic processes of pioneering species and community formation, succession and resource partitioning will be critical for future research involved in microbiome manipulations.
Pleiomorphism in Mycobacterium
Leif A. Kirsebom1, ... Brännvall M. Fredrik Pettersson, in Advances in Applied Microbiology, 2012
5
Regulatory Genes and Spore Formation in the Firmicutes
As discussed above, sporulation has been extensively studied in the Firmicutes, in particular, in B. subtilis, which produce one spore from one mother cell (for reviews, see, e.g., Errington, 2003; Hilbert and Piggot, 2004; Paredes, Alsaker, & Papoutsakis, 2005). However, there are significant variations in sporulation among the different Firmicutes. For example, there are multiple-spore-forming bacteria such as Metabacterium polyspora and Epulopiscium that go through a sporulation pathway as a means of reproduction. Moreover, the phototrophic Heliobacteriumforms endospores with a low frequency in its ecological niche, but when cultivated as a pure culture, it ceases to form spores (Kimble-Long & Madigan, 2001). The hydrogenogen Carboxydothermus hydrogenoformans Z-2901 forms spores despite its lack of many of the known sporulation genes present in B. subtilis (Wu et al., 2005). A comparison of Clostridium acetobutylicum and B. subtilis reveals that the former, which is considered to belong to a more ancestral phylogenetic line than Bacillus, lacks Spo0F and Spo0B. These phosphotransferases are essential for the phosphorylation of Spo0A, the master regulator of the sporulation pathway in the Firmicutes (Dürre, 2011). Phosphorylation of Spo0A in C. acetobutylicum is performed by two alternative, recently identified kinases (Steiner et al., 2011). The data also suggest that there are differences in Clostridiumspp. and B. subtilis with respect to the regulation of expression of the spore-specific σ transcription factors such as the activation of σF by SpoIIE (Bi, Jones, Hess, Tracy, & Papoutsakis, 2011; Jones, Hess, Tracy, & Papoutsakis, 2011). In the future, it will be interesting to find if there are other differences in the sporulation pathway among the Firmicutes.
In the case of Mycobacterium spp., bioinformatics reveals that many of the genes specific for sporulation cannot be identified while some can be (de Hoon, Eichenberger, & Vitkup, 2010; Ghosh et al., 2009; Lamont et al., 2012; Traag et al., 2010). However, most of the orthologue spore genes so far identified also have other functions in the cell; some such examples are presented in Table 4.2. One of the key enzymes in endosporulating bacteria is dipicolinic acid synthase. It is composed of two subunits encoded by spoVFA and spoVFB(Hilbert & Piggot, 2004), both of which are absent in Mycobacterium spp. genomes. Dipicolinc acid (DPA) is also present in S. globisporus (Stastná et al., 1992); R. johrii sp. nov. (Girija et al., 2010); and Clostridium perfringence, Clostridium botulinum, and Clostridium tetani (Paredes et al., 2005). The genes encoding DPA synthase have not been found in any of these bacteria. However, in C. perfringens, the electron-transfer flavoprotein EtfA catalyzes the formation of DPA (Osburn, Melville, & Popham, 2010), showing that there is more than one pathway for the synthesis of DPA in bacteria. Hence, there has to be an alternative DPA synthase, which in Mycobacterium spp. (and other bacteria shown to have DPA, see above) is responsible for the synthesis of DPA.
The spore-specific penicillin-binding protein, PBP 5*, is suggested to be involved in the assembly of the spore cortex in B. subtilis. Deletion of the gene encoding PBP 5*, dacB, does not affect vegetative growth, but spores produced from such a strain are extremely heat sensitive (Buchanan & Gustafson, 1992). Interestingly, a homologue of dacB has been identified in M. tuberculosis, and PknH phosphorylates the DacB protein. The role of DacB in M. tuberculosis is not known, but it is localized in the membrane (Zheng et al., 2007). It will be interesting to understand if DacB in Mycobacterium spp. has a similar role in the assembly process of the cortex as has been described for B. subtilis spores.
Bacillus anthracis and Other Bacillus Species
Christopher K. Cote, ... Susan L. Welkos, in Molecular Medical Microbiology (Second Edition), 2015
Sporulation
Sporulation is a drastic response undertaken by some bacteria, mostly Firmicutes, in response to extreme stress. During sporulation, the growing cell (also referred to as a vegetative cell) will forego normal cellular division to instead form an endospore. The term endospore is derived from the fact that the spore is formed within an intracellular compartment of the mother cell. Once the process is complete, the cell lyses and releases the mature spore into the environment. This is an enormous commitment for the bacterial cell in lieu of normal division. To put it into perspective, the average generation time for a vegetatively growing Bacillus species can be as quick as 25–30 minutes, but the time it takes to complete the formation of a spore is in the range of 6–7 hours. What can induce a bacterial cell to sacrifice itself to make a spore when in the same period of time as many as 14 new generations could have arisen? The most obvious answer from decades of research is starvation. New generations will not arise if there is not useable organic matter in the environment, so when nutrients become extremely limited some genera of bacteria, most notably Bacillus and Clostridium, will sporulate. A fully mature spore is the most durable biological organism currently known, and once formed, it can persist in a harsh environment in a dormant state until conditions later improve.
Sporulation is typically described to occur in seven stages under the control of five sigma (σ) factors that significantly alter the cell on a transcriptional and physiological level [80]. The control of the σ factors exhibits two patterns that dictate gene expression during sporulation over time and within the space of the cell [81,82]. The temporal pattern is a cascade, meaning that activation of one σ factor is required for the later activation of the next. Thus, σ factor expression is timed by being activated in the following order from first to last: σH, σF, σE, σG and σK. As sporulation proceeds, the endospore forms a separate compartment within the mother cell, and each compartment requires a unique set of genes expressed. Accordingly, the triggering of σ factors alternates from one compartment to the next: σH, σE and σK are active in the mother cell, but σF and σGare only active in the developing spore. The details of our current understanding of sporulation and how it is controlled in B. subtilis are presented below.
Identification of the Microbiota in the Aging Process
A. Sarkar*, C.S. Pitchumoni**, in The Microbiota in Gastrointestinal Pathophysiology, 2017
Discrepancies in elderly microbiota
The effect of age on the dominant components of the GM, Firmicutes and Bacteroidetes varies according to nationality and age [21]. Firmicutes, members of the Clostridium cluster XIVa (a dominant group in the intestinal microbiota, which includes among others the species Eubacterium rectale, Eubacterium hallii, Eubacterium ventriosum, C. coccoides, Clostridium symbiosum, Ruminococcus gnavus, Ruminococcus obeum, and the genera Dorea, Roseburia, Lachnospira, Butyrivibrio) were found to decrease in Japanese, Finnish, and Italian elderly and centenarians [5,57,61,62], whereas an inverse trend was found in German old adults [57]. The species F. prausnitzii, belonging to the Clostridium cluster IV (part of Firmicutes phylum), was markedly decreased in Italian elderly and centenarians [5,57], but not confirmed in other European populations [57,63]. However, it is well established that a decline in this antiinflammatory Firmicutes member of the GM is typical of frail, hospitalized, antibiotic- and antiinflammatory-treated elderly [52,64–66]. Conversely, an age related increase in Bacteroidetes was found in German, Austrian, Finnish and Irish elderly [57,61,63,64], but not noted in Italian elderly and centenarians [5,57]. In the case of Irish elderly, Bacteroidetes were found to be the dominant phylum instead of Firmicutes, which has always been regarded as the most abundant in healthy adults [63]. Health-promoting bacteria, such as bifidobacteria, were commonly regarded as decreasing along with ageing [10,57], but the most recent studies do not completely support this [5,51,67]. Much less controversial is the commonly reported age-related increase in facultative anaerobes, including streptococci, staphylococci, enterococci, and enterobacteria [5,49,51,57,61], often classified as pathobionts (bacteria present in the healthy GM in low concentration, which are able to thrive in inflamed conditions) [68].
Streptococcus pyogenes
Mark Reglinski, Shiranee Sriskandan, in Molecular Medical Microbiology (Second Edition), 2015
Classification
Streptococcus pyogenes is a Gram-positive bacterium located within the phylum Firmicutes (Fig. 38.1). Prior to the development of molecular typing techniques, the streptococci were separated into four primary divisions (pyogenic, viridans, lactic and enterococci) based upon their physiological characteristics. The pyogenic division contained species associated with infections in humans and animals, including group A streptococcus (GAS). In modern taxonomy GAS is included within the genus Streptococcus alongside the majority of species included in the pyogenic and viridans divisions [1]. The lactic and enterococcal species have since been reclassified into the genera Lactococcus and Enterococcus, respectively [2,3]. Despite the close historical link between the three genera, the enterococci are genealogically well separated from the streptococci and lactococci, which both belong to the family Streptococcaceae.
Lancefield Grouping
GAS can be differentiated from other human pathogenic streptococci using the Lancefield serological grouping system. This system utilizes type-specific antisera that recognize species-specific ‘Lancefield antigens’ present on the streptococcal cell surface. [1,4]. The ‘type A’ antigen of GAS is a highly conserved surface-expressed polysaccharide, which is uniquely composed of N-acetyl-β-d-glucosamine coupled to a polyrhamnose backbone [5,6]. The term GAS is used here as synonymous with S. pyogenes; however, it should be noted that some other streptococcal species, notably the milleri group, can occasionally express the Lancefield group A carbohydrate and be misidentified as S. pyogenes.
M and emm Typing
GAS isolates are divided into serotypes based on the variable antigenic properties of the major surface M protein. Prior to the development of molecular typing techniques, around 80 serotypes of GAS had been recognized, each of which expressed an immunologically distinct form of the M protein. These serological ‘M types’ could be differentiated using type-specific antisera that were generated using crudely purified M protein from archetypal GAS isolates. [7,8]. The modern approach to M typing (denoted emm typing) involves sequencing of the 5′ variable region of the M protein (emm) gene. This region encodes the heterogeneous N-terminus of the mature protein, which broadly appears to provide the basis for differentiating the classical M serotypes [9]. Of the >200 emm types that have been characterized thus far the ten most prominent account for ~70% of invasive GAS infections [10,11].
M protein molecules can be divided into class I or class II isoforms based on structural differences in the conserved region of the mature protein [12,13]. Class I molecules contain a surface-exposed epitope that is absent from the class II form of the protein and GAS isolates can therefore be classified serologically using commercially available antibody preparations raised against the class I conserved region [4,13]. Serum opacity factor (SOF) typing may also be used to distinguish class I from class II isolates, as only class II strains are opacity factor positive [4].
T and SOF Typing
T protein serotyping and SOF typing are useful adjuncts to M typing. Serum recognition of the T antigen (now identified as the backbone subunit of the pilus protein) can be used to differentiate GAS isolates into ≥20 different T types [14,15]. As there is a strong association between these T types and the classical M types, ‘non-M typable’ strains can often be ascribed a serotype based upon their T antigen reactivity [15,16]. Recently, differentiation of the 20 classical T serotypes by multiplex PCR amplification of the backbone subunit (bp) gene has been shown to be a viable alternative to serological T typing [16]. This process is known as tee typing.
SOF is a high-molecular-weight GAS extracellular protein that opacifies mammalian serum by interacting with high-density lipoproteins [17]. Approximately half of all known GAS M types produce SOF and different M types have been shown to produce immunologically distinct forms of the protein [15]. Anti-SOF antisera can therefore be used to presumptively M type certain GAS isolates through type-specific inhibition of this opacification [18].
Chapter 38 – Streptococcus pyogenes
- Imperial College London, London, UK
- Available online 29 September 2014
Streptococcus pyogenes, also known as group A streptococcus (GAS), is most commonly associated with mild, self-resolving infections of the skin and oropharynx. However, dissemination of the bacteria to normally sterile sites within the body can lead to a variety of invasive conditions that are associated with high morbidity and mortality. In addition, the generation of human cross-reactive antibodies in response to lingering GAS infection can result in the development of post-streptococcal autoimmune sequelae that afflict the organs, joints and CNS.
GAS pathogenesis is mediated by an extensive repertoire of extracellular virulence factors. Initial colonization of the skin and oropharynx is facilitated by cell-associated adhesins that bind to multiple components of the host extracellular matrix. While a battery of antiphagocytic molecules allow the organism to persist at the initial site of infection, the production of multiple toxigenic and tissue-destructive virulence factors facilitates the transition from a superficial to an invasive disease phenotype.
Despite the continuing susceptibility of GAS to β-lactam antibiotics a resurgence of serious streptococcal disease has been observed over the past 30 years. While the cause of this resurgence is incompletely understood it has been tentatively attributed to the reappearance and/or increased circulation of a highly invasive clone of serotype M1T1 GAS. This shift in the epidemiology of GAS infection highlights the need for increased surveillance of GAS in the community, faster, more reliable diagnostic tests for GAS infection in a clinical setting, and more targeted treatments of invasive GAS disease. Above all, the development of a safe, effective GAS vaccine would prove invaluable.
Keywords
- epidemiology;
- group A streptococcus;
- pathogenesis;
- virulence factors
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