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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 -
Annals of Clinical Microbiology and... Apr 2021Bacteroides fragilis is a part of the normal gastrointestinal flora, but it is also the most common anaerobic bacteria causing the infection. It is highly resistant to...
BACKGROUND
Bacteroides fragilis is a part of the normal gastrointestinal flora, but it is also the most common anaerobic bacteria causing the infection. It is highly resistant to antibiotics and contains abundant antibiotic resistance mechanisms.
METHODS
The antibiotic resistance pattern of 78 isolates of B. fragilis (22 strains from clinical samples and 56 strains from the colorectal tissue) was investigated using agar dilution method. The gene encoding Bacteroides fargilis toxin bft, and antibiotic resistance genes were targeted by PCR assay.
RESULTS
The highest rate of resistance was observed for penicillin G (100%) followed by tetracycline (74.4%), clindamycin (41%) and cefoxitin (38.5%). Only a single isolate showed resistance to imipenem which contained cfiA and IS1186 genes. All isolates were susceptible to metronidazole. Accordingly, tetQ (87.2%), cepA (73.1%) and ermF (64.1%) were the most abundant antibiotic-resistant genes identified in this study. MIC values for penicillin, cefoxitin and clindamycin were significantly different among isolates with the cepA, cfxA and ermF in compare with those lacking such genes. In addition, 22.7 and 17.8% of clinical and GIT isolates had the bft gene, respectively.
CONCLUSIONS
The finding of this study shows that metronidazole is highly in vitro active agent against all of B. fragilis isolates and remain the first-line antimicrobial for empirical therapy.
Topics: Anti-Bacterial Agents; Bacterial Toxins; Bacteroides Infections; Bacteroides fragilis; Cefoxitin; Clindamycin; Cross-Sectional Studies; DNA, Bacterial; Drug Resistance, Bacterial; Gastrointestinal Tract; Genes, Bacterial; Humans; Imipenem; Inpatients; Metalloendopeptidases; Metronidazole; Microbial Sensitivity Tests; Penicillin G; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Tetracycline
PubMed: 33892721
DOI: 10.1186/s12941-021-00435-w -
Medical Microbiology and Immunology Jun 2023Bacteroides fragilis is an important etiological agent of serious infections in humans. Rapid methods, readily adaptable to use in medical laboratories, are needed to... (Review)
Review
Bacteroides fragilis is an important etiological agent of serious infections in humans. Rapid methods, readily adaptable to use in medical laboratories, are needed to detect antibiotic resistance and decrease the likelihood of therapy failure. The aim of this study was to determine the prevalence of B. fragilis cfiA-positive isolates. The second purpose was to investigate the carbapenemase activity in B. fragilis strains by Carba NP test. In the study, 5.2% of B. fragilis isolates are phenotypically resistant to meropenem. The cfiA gene was identified in 6.1% of B. fragilis isolates. The MICs of meropenem were significantly higher in cfiA-positive strains. The presence of the cfiA gene along with the IS1186 was detected in one B. fragilis strain which was resistant to meropenem (MIC 1.5 mg/L). The Carba NP test results were positive for all the cfiA-positive strains, including those susceptible to carbapenems based on their MIC values. A review of the literature revealed that the rate of B. fragilis with the cfiA gene varies from 7.6 to 38.9% worldwide. Presented results are in line with the other European studies. Phenotypic testing with the Carba NP test, it seems to be a viable alternative for the cfiA gene detection in B. fragilis isolates. The positive result obtained is of greater clinical importance than the detection of the gene cfiA.
Topics: Humans; Meropenem; Bacteroides fragilis; Bacterial Proteins; Bacterial Infections; Carbapenems; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37178261
DOI: 10.1007/s00430-023-00765-w -
Journal of Bacteriology Jan 2023species can use fumarate and oxygen as terminal electron acceptors during cellular respiration. In the human gut, oxygen diffuses from intestinal epithelial cells...
species can use fumarate and oxygen as terminal electron acceptors during cellular respiration. In the human gut, oxygen diffuses from intestinal epithelial cells supplying "nanaerobic" oxygen levels. Many components of the anaerobic respiratory pathway have been determined, but such analyses have not been performed for nanaerobic respiration. Here, we present genetic, biochemical, enzymatic, and mass spectrometry analyses to elucidate the nanaerobic respiratory pathway in Bacteroides fragilis. Under anaerobic conditions, the transfer of electrons from NADH to the quinone pool has been shown to be contributed by two enzymes, NQR and NDH2. We find that the activity contributed by each under nanaerobic conditions is 77 and 23%, respectively, similar to the activity levels under anaerobic conditions. Using mass spectrometry, we show that the quinone pool also does not differ under these two conditions and consists of a mixture of menaquinone-8 to menaquinone-11, with menaquinone-10 predominant under both conditions. Analysis of fumarate reductase showed that it is synthesized and active under anaerobic and nanaerobic conditions. Previous RNA sequencing data and new transcription reporter assays show that expression of the cytochrome oxidase gene does not change under these conditions. Under nanaerobic conditions, we find both increased CydA protein and increased cytochrome activity. Reduced-minus-oxidized spectra of membranes showed the presence of heme when the bacteria were grown in the presence of protoporphyrin IX and iron under both anaerobic and nanaerobic conditions, suggesting that the active oxidase can be assembled with or without oxygen. By performing a comprehensive analysis of nanaerobic respiration in Bacteroides fragilis, we show that this organism maintains capabilities for anaerobic respiration on fumarate and nanaerobic respiration on oxygen simultaneously. The contribution of the two NADH:quinone oxidoreductases and the composition of the quinone pool are the same under both conditions. Fumarate reductase and cytochrome are both present, and which of these terminal enzymes is active in electron transfer depends on the availability of the final electron acceptor: fumarate or oxygen. The synthesis of cytochrome and fumarate reductase under both conditions serves as an adaptation to an environment with low oxygen concentrations so that the bacteria can maximize energy conservation during fluctuating environmental conditions or occupation of different spatial niches.
Topics: Humans; Bacteroides fragilis; Anaerobiosis; Succinate Dehydrogenase; Vitamin K 2; NAD; Electron Transport; Cytochromes; Quinones; Respiration; Oxygen; Fumarates
PubMed: 36475831
DOI: 10.1128/jb.00389-22 -
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 -
The FEBS Journal Jun 2014Bacteroides fragilis causes the majority of anaerobic infections in humans. The presence of a pathogenicity island in the genome discriminates pathogenic and commensal...
Bacteroides fragilis causes the majority of anaerobic infections in humans. The presence of a pathogenicity island in the genome discriminates pathogenic and commensal B. fragilis strains. The island encodes metalloproteinase II (MPII), a potential virulence protein, and one of three homologous fragilysin isozymes (FRA; also termed B. fragilis toxin or BFT). Here, we report biochemical data on the structural-functional characteristics of the B. fragilis pathogenicity island proteases by reporting the crystal structure of MPII at 2.13 Å resolution, combined with detailed characterization of the cleavage preferences of MPII and FRA3 (as a representative of the FRA isoforms), identified using a high-throughput peptide cleavage assay with 18 583 substrate peptides. We suggest that the evolution of the MPII catalytic domain can be traced to human and archaebacterial proteinases, whereas the prodomain fold is a feature specific to MPII and FRA. We conclude that the catalytic domain of both MPII and FRA3 evolved differently relative to the prodomain, and that the prodomain evolved specifically to fit the B. fragilis pathogenicity. Overall, our data provide insights into the evolution of cleavage specificity and activation mechanisms in the virulent metalloproteinases.
Topics: Bacteroides fragilis; Genomic Islands; Metalloproteases
PubMed: 24698179
DOI: 10.1111/febs.12804 -
BMC Genomics Aug 2022CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems are adaptive immune systems commonly found in prokaryotes that...
BACKGROUND
CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems are adaptive immune systems commonly found in prokaryotes that provide sequence-specific defense against invading mobile genetic elements (MGEs). The memory of these immunological encounters are stored in CRISPR arrays, where spacer sequences record the identity and history of past invaders. Analyzing such CRISPR arrays provide insights into the dynamics of CRISPR-Cas systems and the adaptation of their host bacteria to rapidly changing environments such as the human gut.
RESULTS
In this study, we utilized 601 publicly available Bacteroides fragilis genome isolates from 12 healthy individuals, 6 of which include longitudinal observations, and 222 available B. fragilis reference genomes to update the understanding of B. fragilis CRISPR-Cas dynamics and their differential activities. Analysis of longitudinal genomic data showed that some CRISPR array structures remained relatively stable over time whereas others involved radical spacer acquisition during some periods, and diverse CRISPR arrays (associated with multiple isolates) co-existed in the same individuals with some persisted over time. Furthermore, features of CRISPR adaptation, evolution, and microdynamics were highlighted through an analysis of host-MGE network, such as modules of multiple MGEs and hosts, reflecting complex interactions between B. fragilis and its invaders mediated through the CRISPR-Cas systems.
CONCLUSIONS
We made available of all annotated CRISPR-Cas systems and their target MGEs, and their interaction network as a web resource at https://omics.informatics.indiana.edu/CRISPRone/Bfragilis . We anticipate it will become an important resource for studying of B. fragilis, its CRISPR-Cas systems, and its interaction with mobile genetic elements providing insights into evolutionary dynamics that may shape the species virulence and lead to its pathogenicity.
Topics: Bacteria; Bacteroides fragilis; CRISPR-Associated Proteins; CRISPR-Cas Systems; Genomics; Humans
PubMed: 35953824
DOI: 10.1186/s12864-022-08770-8 -
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 -
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 -
Nature Feb 2024Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes; however, the bacterial gene(s)...
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
Topics: Humans; Acyltransferases; Amidohydrolases; Amines; Bacteroides fragilis; Bile Acids and Salts; Biocatalysis; Cohort Studies; Escherichia coli; Gastrointestinal Microbiome; Ligands; Pregnane X Receptor; Receptors, Aryl Hydrocarbon; Transcription Factors; Infant; Cell Culture Techniques
PubMed: 38326609
DOI: 10.1038/s41586-023-06990-w