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Clinical Microbiology Reviews Oct 2007Bacteroides species are significant clinical pathogens and are found in most anaerobic infections, with an associated mortality of more than 19%. The bacteria maintain a... (Review)
Review
Bacteroides species are significant clinical pathogens and are found in most anaerobic infections, with an associated mortality of more than 19%. The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites. Genomic and proteomic analyses have vastly added to our understanding of the manner in which Bacteroides species adapt to, and thrive in, the human gut. A few examples are (i) complex systems to sense and adapt to nutrient availability, (ii) multiple pump systems to expel toxic substances, and (iii) the ability to influence the host immune system so that it controls other (competing) pathogens. B. fragilis, which accounts for only 0.5% of the human colonic flora, is the most commonly isolated anaerobic pathogen due, in part, to its potent virulence factors. Species of the genus Bacteroides have the most antibiotic resistance mechanisms and the highest resistance rates of all anaerobic pathogens. Clinically, Bacteroides species have exhibited increasing resistance to many antibiotics, including cefoxitin, clindamycin, metronidazole, carbapenems, and fluoroquinolones (e.g., gatifloxacin, levofloxacin, and moxifloxacin).
Topics: Adult; Anti-Bacterial Agents; Bacteroides; Bacteroides Infections; Bacteroides fragilis; Child; Child, Preschool; Drug Resistance, Bacterial; Gastrointestinal Tract; Humans; Infant; Infant, Newborn; Microbial Sensitivity Tests; Virulence
PubMed: 17934076
DOI: 10.1128/CMR.00008-07 -
Journal of Immunology Research 2014Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis and is a member of more than 500 bacterial species that... (Review)
Review
Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis and is a member of more than 500 bacterial species that live in the oral cavity. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions: this is attributed to its arsenal of specialized virulence factors. The purpose of this review is to provide an overview of one of the main periodontal pathogens-Porphyromonas gingivalis. This bacterium, along with Treponema denticola and Tannerella forsythia, constitute the "red complex," a prototype polybacterial pathogenic consortium in periodontitis. This review outlines Porphyromonas gingivalis structure, its metabolism, its ability to colonize the epithelial cells, and its influence upon the host immunity.
Topics: Bacteroidaceae Infections; Humans; Periodontitis; Porphyromonas gingivalis
PubMed: 24741603
DOI: 10.1155/2014/476068 -
Scientific Reports Sep 2020Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most... (Clinical Trial)
Clinical Trial
Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
Topics: Bacteroides; Feces; Female; Gastrointestinal Microbiome; Humans; Ileum; Intestinal Mucosa; Intestine, Large; Male
PubMed: 32917913
DOI: 10.1038/s41598-020-71939-2 -
ELife Nov 2013Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for...
Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.001.
Topics: Adult; Animals; Arthritis, Rheumatoid; Bacteroidaceae Infections; Disease Models, Animal; Female; Genome, Bacterial; Humans; Male; Mice; Mice, Inbred C57BL; Prevotella
PubMed: 24192039
DOI: 10.7554/eLife.01202 -
Cell Host & Microbe Sep 2009The human gut microbiota is a metabolic organ whose cellular composition is determined by a dynamic process of selection and competition. To identify microbial genes...
The human gut microbiota is a metabolic organ whose cellular composition is determined by a dynamic process of selection and competition. To identify microbial genes required for establishment of human symbionts in the gut, we developed an approach (insertion sequencing, or INSeq) based on a mutagenic transposon that allows capture of adjacent chromosomal DNA to define its genomic location. We used massively parallel sequencing to monitor the relative abundance of tens of thousands of transposon mutants of a saccharolytic human gut bacterium, Bacteroides thetaiotaomicron, as they established themselves in wild-type and immunodeficient gnotobiotic mice, in the presence or absence of other human gut commensals. In vivo selection transforms this population, revealing functions necessary for survival in the gut: we show how this selection is influenced by community composition and competition for nutrients (vitamin B(12)). INSeq provides a broadly applicable platform to explore microbial adaptation to the gut and other ecosystems.
Topics: Animals; Bacteroides; Gastrointestinal Tract; Germ-Free Life; Humans; Mice; Phylogeny; Symbiosis
PubMed: 19748469
DOI: 10.1016/j.chom.2009.08.003 -
Trends in Microbiology Jan 2021Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of... (Review)
Review
Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of periodontitis. Transposon sequencing has been employed to define the core essential genome of this bacterium and genes conditionally essential in multiple environments - abscess formation; epithelial colonization; and cigarette smoke toxin exposure; as well as to elucidate genes required for iron acquisition and a functional type 9 secretion system. Validated and predicted protein catabolism genes identified include a combination of established virulence factors and a larger set of seemingly more mundane proteolytic genes. The functions and relevance of genes that share essentiality in multiple disease-relevant conditions are examined. These common stress-related genes may represent particularly attractive therapeutic targets for the control of P. gingivalis infections.
Topics: Animals; Bacterial Proteins; Bacteroidaceae Infections; Genes, Essential; Humans; Porphyromonas gingivalis; Virulence Factors
PubMed: 33071035
DOI: 10.1016/j.tim.2020.09.002 -
Microbiology (Reading, England) Jul 2021Capsular polysaccharides (CPSs) protect bacteria from host and environmental factors. Many bacteria can express different CPSs and these CPSs are phase variable. For...
Capsular polysaccharides (CPSs) protect bacteria from host and environmental factors. Many bacteria can express different CPSs and these CPSs are phase variable. For example, ) is a prominent member of the human gut microbiome and expresses eight different capsular polysaccharides. Bacteria, including , have been shown to change their CPSs to adapt to various niches such as immune, bacteriophage, and antibiotic perturbations. However, there are limited tools to study CPSs and fundamental questions regarding phase variance, including if gut bacteria can express more than one capsule at the same time, remain unanswered. To better understand the roles of different CPSs, we generated a CPS1-specific antibody and a flow cytometry assay to detect CPS expression in individual bacteria in the gut microbiota. Using these novel tools, we report for the first time that bacteria can simultaneously express multiple CPSs. We also observed that nutrients such as glucose and salts had no effect on CPS expression. The ability to express multiple CPSs at the same time may provide bacteria with an adaptive advantage to thrive amid changing host and environmental conditions, especially in the intestine.
Topics: Bacterial Capsules; Bacteroides thetaiotaomicron; Gastrointestinal Microbiome; Humans; Polysaccharides, Bacterial
PubMed: 34224345
DOI: 10.1099/mic.0.001066 -
Proceedings of the National Academy of... Sep 2023Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial...
Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial community robustness and resiliency in health and disease. This knowledge is foundational for development of microbiota-directed therapeutics. To model how bacteria prioritize glycans in the gut, germfree mice were colonized with 13 human gut bacterial strains, including seven saccharolytic species. Animals were fed a Western diet supplemented with pea fiber. After community assembly, an inducible CRISPR-based system was used to selectively and temporarily reduce the absolute abundance of or by 10- to 60-fold. Each knockdown resulted in specific, reproducible increases in the abundances of other and dynamic alterations in their expression of genes involved in glycan utilization. Emergence of these "alternate consumers" was associated with preservation of community saccharolytic activity. Using an inducible system for CRISPR base editing in vitro, we disrupted translation of transporters critical for utilizing dietary polysaccharides in , a knockdown-responsive taxon. In vitro and in vivo tests of the resulting mutants allowed us to further characterize mechanisms associated with its increased fitness after knockdown. In principle, the approach described can be applied to study utilization of a range of nutrients and to preclinical efforts designed to develop therapeutic strategies for precision manipulation of microbial communities.
Topics: Humans; Animals; Mice; Bacteroides; Polysaccharides; Bacteroides thetaiotaomicron; Biological Assay; Diet, Western
PubMed: 37733741
DOI: 10.1073/pnas.2311422120 -
Microbiology Spectrum Dec 2021The emergence of (X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) (X) positive samples from 12,829 human...
The emergence of (X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) (X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from worldwide. These (X) genes were dominated by (X2)-like orthologs but we also identified 12 samples carrying novel (X) genes, designed (X45), (X46), and (X47), were resistant to tigecycline. The metagenomic analysis indicated these (X) genes distributed in anaerobes dominated by (78.89%) of human-gut origin. Two mobile elements IS and IS were most likely to promote the transmission of these (X2)-like orthologs between and Riemerella anatipestifer. (X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant genes (X45), (X46), and (X47). Further tracing these (X) in single bacterial isolate from public repository indicated (X) genes were present as early as 1960s in R. anatipestifer that was the primary (X) carrier at early stage (before 2000). The (X2) and non-(X2) orthologs were primarily distributed in humans and food animals respectively, and non-(X2) were dominated by (X3) and (X4). Genomic comparison indicated these (X) genes were likely to be generated during (X) transmission between and E. coli/Acinetobacter spp., and IS played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of (X). In addition, of human-gut origin was an important hidden reservoir and mutational incubator for the mobile (X) genes that enabled spread to facultative anaerobes and aerobes. The emergence of the tigecycline resistance gene (X) has posed a severe threat to public health. However, reports of its origin and distribution in human remain rare. Here, we explore the origin and distribution of (X) from large-scale metagenomic data of human-gut origin and public repository. This study revealed the emergency of (X) gene in 1960s, which has refreshed a previous standpoint that the earliest presence of (X) was in 1980s. The metagenomic analysis from data mining covered the unculturable bacteria, which has overcome the traditional bacteria isolating and purificating technologies, and the analysis indicated that the of human-gut origin was an important hidden reservoir for (X) that enabled spread to facultative anaerobes and aerobes. The continuous monitoring of mobile tigecycline resistance determinants from both culturable and unculturable microorganisms is imperative for understanding and tackling the dissemination of (X) genes in both the health care and agricultural sectors.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Bacteroidaceae; DNA Transposable Elements; Drug Resistance, Bacterial; Escherichia coli; Flavobacteriaceae; Gene Transfer, Horizontal; Humans; Microbial Sensitivity Tests; Plasmids; Riemerella; Tigecycline
PubMed: 34935428
DOI: 10.1128/Spectrum.01164-21 -
Future Microbiology 2015Porphyromonas gingivalis is one of the keystone pathogens associated with chronic periodontitis. All P. gingivalis strains examined thus far produce outer membrane... (Review)
Review
Porphyromonas gingivalis is one of the keystone pathogens associated with chronic periodontitis. All P. gingivalis strains examined thus far produce outer membrane vesicles. Recent studies have found that vesicles possess some well-known virulence factors of P. gingivalis such as adhesins, toxins and proteolytic enzymes. Carrying most of the characteristic features of their parent P. gingivalis cells, vesicles communicate with host cells and other members of microbial biofilms, resulting in the transmission of virulence factors into these host cells and the formation of pathogenic bacteria-dominated microbial communities. An in-depth understanding of both the nature and role of vesicles in the pathogenicity of P. gingivalis is both important and timely, particularly when speaking of periodontitis and its related systemic effects.
Topics: Adhesins, Bacterial; Biofilms; Humans; Microbial Consortia; Organelle Biogenesis; Periodontitis; Porphyromonas gingivalis; Transport Vesicles; Virulence Factors
PubMed: 26343879
DOI: 10.2217/fmb.15.63