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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 -
Microbiology (Reading, England) Apr 2022is an obligately anaerobic Gram-negative bacterium and a major colonizer of the human large colon where is a predominant genus. During the growth of an individual... (Review)
Review
is an obligately anaerobic Gram-negative bacterium and a major colonizer of the human large colon where is a predominant genus. During the growth of an individual clonal population, an astonishing number of reversible DNA inversion events occur, driving within-strain diversity. Additionally, the pan-genome contains a large pool of diverse polysaccharide biosynthesis loci, DNA restriction/modification systems and polysaccharide utilization loci, which generates remarkable between-strain diversity. Diversity clearly contributes to the success of within its normal habitat of the gastrointestinal (GI) tract and during infection in the extra-intestinal host environment. Within the GI tract, is usually symbiotic, for example providing localized nutrients for the gut epithelium, but within the GI tract may not always be benign. Metalloprotease toxin production is strongly associated with colorectal cancer. is unique amongst bacteria; some strains export a protein >99 % structurally similar to human ubiquitin and antigenically cross-reactive, which suggests a link to autoimmune diseases. is not a primary invasive enteric pathogen; however, if colonic contents contaminate the extra-intestinal host environment, it successfully adapts to this new habitat and causes infection; classically peritoneal infection arising from rupture of an inflamed appendix or GI surgery, which if untreated, can progress to bacteraemia and death. In this review selected aspects of adaptation to the different habitats of the GI tract and the extra-intestinal host environment are considered, along with the considerable challenges faced when studying this highly variable bacterium.
Topics: Bacterial Infections; Bacteroides fragilis; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Microbiota; Polysaccharides
PubMed: 35404220
DOI: 10.1099/mic.0.001156 -
Microbiological Research May 2018The resistance of Bacteroides fragilis to the most antimicrobial agents has been reported in the world. Identification of the microbial resistance mechanisms can play an... (Review)
Review
The resistance of Bacteroides fragilis to the most antimicrobial agents has been reported in the world. Identification of the microbial resistance mechanisms can play an important role in controlling these resistances. Currently, B. fragilis is resistant to most antibiotics. The multi-drug efflux pumps have been shown to underlie the antimicrobial resistance in B. fragilis strains. Two types of these efflux pumps including RND and MATE can be regarded as main structures responsible for antibiotic resistance. Therefore, the strategy for suppressing of this efflux system may be useful in the treatment and control of the multidrug-resistant B. fragilis. The purpose of this study is to review the B. fragilis efflux pumps and their functions in the resistance to antibiotics.
Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacteroides fragilis; Biological Transport, Active; Databases, Factual; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Humans; Membrane Transport Proteins
PubMed: 29625653
DOI: 10.1016/j.micres.2018.02.007 -
PLoS Pathogens Dec 2020
Review
Topics: Bacterial Infections; Bacteroides fragilis; Genetic Variation; Humans; Microbiota
PubMed: 33301530
DOI: 10.1371/journal.ppat.1009056 -
Journal of Molecular Biology Feb 2020The human gut is colonized by hundreds of trillions of microorganisms whose acquisition begins during early infancy. Species from the Bacteroides genus are ubiquitous... (Review)
Review
The human gut is colonized by hundreds of trillions of microorganisms whose acquisition begins during early infancy. Species from the Bacteroides genus are ubiquitous commensals, comprising about thirty percent of the human gut microbiota. Bacteroides fragilis is one of the least abundant Bacteroides species, yet is the most common anaerobe isolated from extraintestinal infections in humans. A subset of B. fragilis strains carry a genetic element that encodes a metalloprotease enterotoxin named Bacteroides fragilis toxin, or BFT. Toxin-bearing strains, or Enterotoxigenic B. fragilis (ETBF) cause acute and chronic intestinal disease in children and adults. Despite this association with disease, around twenty percent of the human population appear to be asymptomatic carriers of ETBF. BFT damages the colonic epithelial barrier by inducing cleavage of the zonula adherens protein E-cadherin and initiating a cell signaling response characterized by inflammation and c-Myc-dependent pro-oncogenic hyperproliferation. As a consequence, mice harboring genetic mutations that predispose to colonic inflammation or tumor formation are uniquely susceptible to toxin-mediated injury. The recent observation of ETBF-bearing biofilms in colon biopsies from humans with colon cancer susceptibility loci strongly suggests that ETBF is a driver of colorectal cancer. This article will address ETBF biology from a host-pathobiont perspective, including clinical data, analysis of molecular mechanisms of disease, and the complex ecological context of the human gut.
Topics: Animals; Bacteroides fragilis; Genomics; Humans; Metabolomics; Microscopy, Electron; Proteomics
PubMed: 31857085
DOI: 10.1016/j.jmb.2019.12.003 -
Anaerobe 2006Bacteroides fragilis is an anaerobic commensal constituting only 1-2% of the micro-flora of the human gastrointestinal tract, yet it is the predominant anaerobic isolate... (Review)
Review
Bacteroides fragilis is an anaerobic commensal constituting only 1-2% of the micro-flora of the human gastrointestinal tract, yet it is the predominant anaerobic isolate in cases of intraabdominal sepsis and bacteremia. B. fragilis can play two roles in the host: in its role as friendly commensal, it must be able to establish itself in the host intestinal mucosa, to utilize and process polysaccharides for use by the host, and to resist the noxious effects of bile salts. In its role as pathogen, it must be able to attach itself to the site of infection, evade killing mechanisms by host defense, withstand antimicrobial treatment and produce factors that damage host tissue. The cell envelope of B. fragilis, likewise, must be able to function in the roles of aggressor, defender and strategist in allowing the organism to establish itself in the host--whether as friend or foe. Recent studies of the genomes and proteomes of the genus Bacteroides suggest that these organisms have evolved strategies to survive and dominate in the overcrowded gastrointestinal neighborhood. Analysis of the proteomes of B. fragilis and Bacteroides thetaiotaomicron demonstrates both a tremendous capacity to use a wide range of dietary polysaccharides, and the capacity to create variable surface antigenicities by multiple DNA inversion systems. The latter characteristic is particularly pronounced in the species B. fragilis, which is more frequently found at the mucosal surface (i.e., often the site of attack by host defenses). The B. fragilis cell envelope undergoes major protein expression and ultrastructural changes in response to stressors such as bile or antimicrobial agents. These agents may also act as signals for attachment and colonization. Thus the bacterium manages its surface characteristics to enable it to bind to its target, to use the available nutrients, and to avoid or evade hostile forces (host-derived or external) in its multiple roles.
Topics: Bacterial Capsules; Bacterial Outer Membrane Proteins; Bacteroides Infections; Bacteroides fragilis; Bile; Drug Resistance, Multiple, Bacterial; Fimbriae, Bacterial; Humans; Intestines
PubMed: 17045496
DOI: 10.1016/j.anaerobe.2006.09.004 -
Toxicon : Official Journal of the... Nov 2001Bacteroides fragilis are both key commensals and important human pathogens. Particular strains of B. fragilis, termed enterotoxigenic B. fragilis (ETBF), are recently... (Review)
Review
Bacteroides fragilis are both key commensals and important human pathogens. Particular strains of B. fragilis, termed enterotoxigenic B. fragilis (ETBF), are recently identified enteric pathogens of children and adults. These strains are distinguished by secretion of a 20kDa metalloprotease toxin (B. fragilis toxin or BFT), the first recognized and only established toxin to date for B. fragilis. Three isotypes of BFT are encoded by distinct bft loci contained within a 6kb chromosomal region unique to ETBF strains termed the B. fragilis pathogenicity island (BfPAI). Experimental studies have suggested that the cellular target for BFT is E-cadherin, the primary protein of the zonula adherens. It is postulated that BFT cleavage of E-cadherin is critical in precipitating the intracellular events culminating in the two established activities for BFT; namely, stimulation of secretion in ligated intestinal segments in several animal species and alteration of cellular morphology only in epithelial cells that retain the ability to polarize and form a tight junctional complex. Future studies will be directed to characterizing in greater detail both the molecular genetics of the BFT toxin and the precise steps in its cellular mechanism of action.
Topics: Animals; Bacterial Toxins; Bacteroides Infections; Bacteroides fragilis; Humans; Metalloendopeptidases
PubMed: 11595636
DOI: 10.1016/s0041-0101(01)00160-x -
Clinical Microbiology Reviews Apr 2009Enterotoxigenic Bacteroides fragilis (ETBF) strains are strains of B. fragilis that secrete a 20-kDa heat-labile zinc-dependent metalloprotease toxin termed the B.... (Review)
Review
Enterotoxigenic Bacteroides fragilis (ETBF) strains are strains of B. fragilis that secrete a 20-kDa heat-labile zinc-dependent metalloprotease toxin termed the B. fragilis toxin (BFT). BFT is the only recognized virulence factor specific for ETBF. ETBF strains are associated with inflammatory diarrheal disease in children older than 1 year of age and in adults; limited data suggest an association of ETBF colonization with inflammatory bowel disease flare-ups and colorectal cancer. ETBF secretes one of three highly related BFT isoforms. The relationship between BFT isoform and disease expression is unknown. Although the mechanism of action of BFT is incompletely understood, available data suggest that BFT binds to a specific intestinal epithelial cell receptor, stimulating intestinal cell signal transduction pathways that result in cell morphology changes, cleavage of E-cadherin, reduced colonic barrier function, and increased epithelial cell proliferation and cytokine expression (such as the proinflammatory chemokine interleukin-8). Together, the data suggest that in some hosts, ETBF acts via secretion of BFT to induce colitis. However, the full spectrum of clinical disease related to ETBF and the impact of chronic ETBF colonization on the host remain to be defined.
Topics: Animals; Bacterial Toxins; Bacteroides Infections; Bacteroides fragilis; Humans
PubMed: 19366918
DOI: 10.1128/CMR.00053-08 -
Food Research International (Ottawa,... Dec 2019Bacteroides fragilis (B. fragilis) is a commensal Gram-negative obligate anaerobe that resides in the mammalian lower gut and can profoundly affect the susceptibility of... (Review)
Review
Bacteroides fragilis (B. fragilis) is a commensal Gram-negative obligate anaerobe that resides in the mammalian lower gut and can profoundly affect the susceptibility of the host to inflammatory diseases. Previous studies have identified B. fragilis as a common opportunistic pathogen in clinical infections and suggested that it may be responsible for a range of diseases involving a permeable intestinal barrier. However, recent studies of the relationship between nontoxigenic B. fragilis and the immune system have indicated that several B. fragilis strains may be potential probiotic. In the present review, we summarize the factors influencing the intestinal abundance of B. fragilis and discuss the biological interactions between this microbe and the host. Immune system development, age, individual dietary habits, physical condition, drug intake and personal lifestyle habits can all affect the abundance of B. fragilis in the human intestine. Polysaccharide A or outer membrane vesicles from nontoxigenic B. fragilis may mediate beneficial interactions with the host, whereas enterotoxigenic B. fragilis toxin or lipopolysaccharide may stimulate colitis or even systemic inflammation. Generally, this review summarizes the biological characteristics of B. fragilis and describes future application of probiotics.
Topics: Animals; Bacterial Toxins; Bacteroides Infections; Bacteroides fragilis; Central Nervous System Diseases; Colitis; Colorectal Neoplasms; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Immunomodulation; Metalloendopeptidases; Probiotics; Symbiosis
PubMed: 31732047
DOI: 10.1016/j.foodres.2019.108590 -
Frontiers in Cellular and Infection... 2019Enterotoxigenic (ETBF) produces toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC). In experimental models,...
Enterotoxigenic (ETBF) produces toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC). In experimental models, ETBF has been shown to contribute to colon carcinogenesis. The present study was conducted to investigate mucosal colonization of ETBF in the colon to find a possible association between the presence of ETBF and precancerous and cancerous lesions. The mucosal biopsies of involved sites were obtained from 68 patients with precancerous and cancerous lesions and 52 healthy controls (HC). The samples were cultured on Bacteroides Bile Esculin agar. Then, specific primers were designed to detect and gene using quantitative real-time PCR, and the possible links of ETBF with clinicopathological characteristics was evaluated. Also real-time PCR was performed to detect the gene subtypes. was detected in 51% of the patients and 48% of HCs cultures. The 16SrRNA gene was found to be present in 63 and 81% of the patients and HCs' samples, respectively. Moreover, the gene was detected in 47 and 3.8% of the patients and HCs, respectively. Also, was significantly more abundant in the patients' samples compared to those of HCs. In the patient group, higher odds ratio (OR) of ETBF was significantly associated with serrated lesions and adenoma with low-grade dysplasia. The gene was the most prevalent subtype of , followed by the gene. This was the first study in Iran to demonstrate increased positivity of ETBF in patients with precancerous and cancerous lesions. In this study, the gene was found to be associated with CRC, especially in the patients with precancerous lesions and initial carcinogenic lesions. Moreover, the results suggest that mucosal BFT exposure is common and could be a risk factor and a screening marker for developing CRC.
Topics: Adult; Aged; Bacteria; Bacterial Toxins; Bacteroides Infections; Bacteroides fragilis; Colon; Colorectal Neoplasms; Female; Humans; Iran; Male; Metalloendopeptidases; Middle Aged; Precancerous Conditions; RNA, Ribosomal, 16S; Real-Time Polymerase Chain Reaction
PubMed: 32010637
DOI: 10.3389/fcimb.2019.00449