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Gut Microbes 2021The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of... (Review)
Review
The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host. However, beneficial gut organisms can also be pathogenic when present in the gut or other locations in the body. Among dominant beneficial bacteria are several species of , which metabolize polysaccharides and oligosaccharides, providing nutrition and vitamins to the host and other intestinal microbial residents. These topics and the specific organismal and molecular interactions that are known to be responsible for the beneficial and detrimental effects of species in humans comprise the focus of this review. The complexity of these interactions will be revealed.
Topics: Animals; Bacteroides; Extracellular Vesicles; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Microbial Interactions; Polysaccharides; Virulence Factors
PubMed: 33535896
DOI: 10.1080/19490976.2020.1848158 -
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 -
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 -
Microbiome Feb 2019Bacteria within family S24-7 (phylum Bacteroidetes) are dominant in the mouse gut microbiota and detected in the intestine of other animals. Because they had not been...
BACKGROUND
Bacteria within family S24-7 (phylum Bacteroidetes) are dominant in the mouse gut microbiota and detected in the intestine of other animals. Because they had not been cultured until recently and the family classification is still ambiguous, interaction with their host was difficult to study and confusion still exists regarding sequence data annotation.
METHODS
We investigated family S24-7 by combining data from large-scale 16S rRNA gene analysis and from functional and taxonomic studies of metagenomic and cultured species.
RESULTS
A total of 685 species was inferred by full-length 16S rRNA gene sequence clustering. While many species could not be assigned ecological habitats (93,045 samples analyzed), the mouse was the most commonly identified host (average of 20% relative abundance and nine co-occurring species). Shotgun metagenomics allowed reconstruction of 59 molecular species, of which 34 were representative of the 16S rRNA gene-derived species clusters. In addition, cultivation efforts allowed isolating five strains representing three species, including two novel taxa. Genome analysis revealed that S24-7 spp. are functionally distinct from neighboring families and versatile with respect to complex carbohydrate degradation.
CONCLUSIONS
We provide novel data on the diversity, ecology, and description of bacterial family S24-7, for which the name Muribaculaceae is proposed.
Topics: Animals; Bacteriological Techniques; Bacteroides; Biodiversity; DNA, Bacterial; DNA, Ribosomal; Gastrointestinal Microbiome; Metagenomics; Mice; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Species Specificity
PubMed: 30782206
DOI: 10.1186/s40168-019-0637-2 -
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 -
Microbiology Spectrum Apr 2015Bacteroides species are one of the most prevalent groups of bacteria present in the human colon. Many strains carry large, integrated elements including integrative and... (Review)
Review
Bacteroides species are one of the most prevalent groups of bacteria present in the human colon. Many strains carry large, integrated elements including integrative and conjugative elements (ICEs). One such ICE is CTnDOT, which is 65 kb in size and encodes resistances to tetracycline and erythromycin. CTnDOT has been increasing in prevalence in Bacteroides spp., and is now found in greater than 80% of natural isolates. In recent years, CTnDOT has been implicated in the spread of antibiotic resistance among gut microbiota. Interestingly, the excision and transfer of CTnDOT is stimulated in the presence of tetracycline. The tyrosine recombinase IntDOT catalyzes the integration and excision reactions of CTnDOT. Unlike the well-characterized lambda Int, IntDOT tolerates heterology in the overlap region between the sites of cleavage and strand exchange. IntDOT also appears to have a different arrangement of active site catalytic residues. It is missing one of the arginine residues that is conserved in other tyrosine recombinases. The excision reaction of CTnDOT is complex, involving excision proteins Xis2c, Xis2d, and Exc, as well as IntDOT and a Bacteroides host factor. Xis2c and Xis2d are small, basic proteins like other recombination directionality factors (RDFs). Exc is a topoisomerase; however, the topoisomerase function is not required for the excision reaction. Exc has been shown to stimulate excision frequencies when there are mismatches in the overlap regions, suggesting that it may play a role in resolving Holliday junctions (HJs) containing heterology. Work is currently under way to elucidate the complex interactions involved with the formation of the CTnDOT excisive intasomes.
Topics: Bacteroides; DNA Topoisomerases; Drug Resistance, Bacterial; Gastrointestinal Tract; Gene Expression Regulation, Bacterial; Genes, Bacterial; Humans; Interspersed Repetitive Sequences; Recombinases; Recombination, Genetic; Tetracycline
PubMed: 26104696
DOI: 10.1128/microbiolspec.MDNA3-0020-2014 -
Nature Communications Oct 2023Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the... (Meta-Analysis)
Meta-Analysis
Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the contribution of specific bacteria to the risk of severe malaria is unknown. Here, multiomics approaches demonstrate that specific species of Bacteroides are causally linked to the risk of severe malaria. Plasmodium yoelii hyperparasitemia-resistant mice gavaged with murine-isolated Bacteroides fragilis develop P. yoelii hyperparasitemia. Moreover, Bacteroides are significantly more abundant in Ugandan children with severe malarial anemia than with asymptomatic P. falciparum infection. Human isolates of Bacteroides caccae, Bacteroides uniformis, and Bacteroides ovatus were able to cause susceptibility to severe malaria in mice. While monocolonization of germ-free mice with Bacteroides alone is insufficient to cause susceptibility to hyperparasitemia, meta-analysis across multiple studies support a main role for Bacteroides in susceptibility to severe malaria. Approaches that target gut Bacteroides present an opportunity to prevent severe malaria and associated deaths.
Topics: Child; Humans; Animals; Mice; Microbial Consortia; Malaria; Bacteroides; Bacteroides fragilis; Anemia; Plasmodium yoelii
PubMed: 37833304
DOI: 10.1038/s41467-023-42235-0 -
Cell Host & Microbe Feb 2022Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably...
Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably Bacteroides, contain numerous PULs that enable glycan utilization and shape ecological dynamics. To investigate the role of PULs on fitness and inter-species interactions, we develop a CRISPR-based genome editing tool to study 23 PULs in Bacteroides uniformis (BU). BU PULs show distinct glycan-degrading functions and transcriptional coordination that enables the population to adapt upon loss of other PULs. Exploiting a BU mutant barcoding strategy, we demonstrate that in vitro fitness and BU colonization in the murine gut are enhanced by deletion of specific PULs and modulated by glycan availability. PULs mediate glycan-dependent interactions with butyrate producers that depend on the degradation mechanism and glycan utilization ability of the butyrate producer. Thus, PULs determine community dynamics and butyrate production and provide a selective advantage or disadvantage depending on the nutritional landscape.
Topics: Animals; Bacterial Proteins; Bacteroides; Gastrointestinal Microbiome; Genes, Bacterial; Genetic Fitness; Humans; Mice; Polysaccharides
PubMed: 34995484
DOI: 10.1016/j.chom.2021.12.006 -
Molecular Microbiology Jan 2022Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions,...
Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA-binding proteins and predict a Bacteroides cold-shock protein homolog to have an RNA-related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members.
Topics: Bacterial Proteins; Bacteroides; Bacteroides thetaiotaomicron; Computational Biology; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Genomics; RNA, Bacterial; RNA, Small Untranslated; RNA-Binding Proteins; Synteny
PubMed: 34379855
DOI: 10.1111/mmi.14793 -
The Journal of Antimicrobial... May 2022We sought to characterize the carbapenem resistance mechanism of Bacteroides xylanisolvens 14880, an imipenem-resistant strain from Germany, and assess its prevalence.
OBJECTIVES
We sought to characterize the carbapenem resistance mechanism of Bacteroides xylanisolvens 14880, an imipenem-resistant strain from Germany, and assess its prevalence.
METHODS
Antimicrobial susceptibilities were determined using agar dilution or Etest methodology and specific imipenemase activity was detected. The genomic sequence of B. xylanisolvens 14880 was determined and analysed for antibiotic resistance genes and genomic islands. We also used gene transfer to a carbapenem susceptible host, along with 5'-RACE, conventional PCR with capillary sequencing and RT-PCR-based screening.
RESULTS
B. xylanisolvens 14880 displayed resistance to carbapenems and produced high specific imipenemase activity. Its genomic sequence was 6.1 Mbp and a class B1 β-lactamase gene (termed crxA) was detected in it. crxA was carried on a putative genomic island with insertion sequence (IS) elements and a putative GNAT (Gcn5-like acetyltransferase) toxin gene. Promoter localization by 5'-RACE and gene targeting to an imipenem-susceptible Bacteroides host indicated that it is activated by an IS1380-like IS element and it can confer carbapenem resistance. The PCR screening of Bacteroides strains showed that crxA was specific to B. xylanisolvens with a carriage rate of 16.7%.
CONCLUSIONS
B. xylanisolvens strains can harbour a carbapenem resistance gene, which has many similarities to the 'cfiA system': metallo-β-lactamase (MBL), IS element activation, carriage of a GNAT toxin gene, specific for a unique Bacteroides species with a significant prevalence.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Bacteroides; Bacteroides fragilis; Carbapenems; DNA Transposable Elements; Genomics; Imipenem; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 35296904
DOI: 10.1093/jac/dkac088