Genetic Diversity of the Capsular Polysaccharide C Biosynthesis Region of Bacteroides fragilis

Comstock, Laurie E.; Pantosti, Annalisa; Kasper, Dennis L.

doi:10.1128/.68.11.6182-6188.2000

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, not all non-enterotoxigenic strains ameliorate DSS-induced colitis and some strains even skew macrophages to take on a pro-inflammatory M1-phenotype 18,32 . Furthermore, capsular polysaccharides are distinct between strains of Bacteroides fragilis 33 . We have shown that between B. fragilis strains, the genetic composition of PAP B. fragilis p207 and strain 9343, are genetically-distinct, suggesting that they may have distinct immunomodulatory properties (Figure S6).…”

Section: Discussionmentioning

confidence: 99%

Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases

Shan,

Lake,

Cham

et al. 2023

Preprint

View full text Add to dashboard Cite

Inflammatory bowel diseases (IBD) arise from a convergence of underlying genetic susceptibility, environmental factors, and shifts in gut microbiota function and membership. Although the latter may trigger and contribute to IBD, there is little consensus on a specific causative pathogen. In this study, we demonstrate that commensalBacteroides fragilisstrains from ulcerative colitis (UC) patients before and during the development of ileal pouchitis engraft and promote colitis in specific pathogen free (SPF) IL-10 deficient (IL-10-/-) mice, but not in wild type SPF mice or when mono-associated in germ free mice. The colitis in IL-10-/-mice was also associated with significant alterations in commensal microbiota potentially important for maintaining intestinal and immune homeostasis. UC pouchitisB. fragilisalso engrafts in DSS-induced colitis in WT SPF mice, indicating a fitness advantage under conditions of mucosal inflammation over other commensals in the gut microbiota. These findings show that gut inflammation promotes the expansion and fitness of UC-derivedBacteroidesspecies that is associated with changes in the SPF gut microbiota and may be promote colitis in genetically susceptible hosts.ImportanceThis study supports the notion that human inflammatory bowel diseases arise from the emergence of indigenous pathobionts in genetically-prone subjects. Colitis-promoting pathobionts are well-suited to establish themselves in the host inflammatory environment and outcompete endogenous microbiota. Once engrafted, the pathobiont can further aggravate inflammation in a genetically-susceptible host. Such complex interplay among several factors creates a vicious pro-inflammatory cycle and promotes disease development. These findings are consistent with our previous clinical observation thatB. fragilis, an otherwise low-abundance commensal species, expands prior to the development of UC pouchitis. We believe these findings are relevant to the pathogenesis of UC pouchitis and possibly human inflammatory bowel diseases in general, underscoring the role of commensal to pathobiont transitions, rather than classical pathogens, in promoting and exacerbating the onset of human IBD.

show abstract

Section: Discussionmentioning

confidence: 99%

Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases

Shan,

Lake,

Cham

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

A Family of Transcriptional Antitermination Factors Necessary for Synthesis of the Capsular Polysaccharides of Bacteroides fragilis

2009

Self Cite

View full text Add to dashboard Cite

A single strain of Bacteroides fragilis synthesizes eight distinct capsular polysaccharides, designated PSA to PSH. These polysaccharides are synthesized by-products encoded by eight separate polysaccharide biosynthesis loci. The genetic architecture of each of these eight loci is similar, including the fact that the first gene of each locus is a paralog of the first gene of each of the other PS loci. These proteins are designated the UpxY family, where x is replaced by a to h, depending upon the polysaccharide locus from which it is produced. Mutational analysis of three separate upxY genes demonstrated that they are necessary and specific for transcription of their respective polysaccharide biosynthesis operon and that they function in trans. Transcriptional reporter constructs, reverse transcriptase PCR, and deletion analysis demonstrated that the UpxYs do not affect initiation of transcription, but rather prevent premature transcriptional termination within the 5 untranslated region between the promoter and the upxY gene. The UpxYs have conserved motifs that are present in NusG and NusG-like proteins. Mutation of two conserved residues within the conserved KOW motif abrogated UpaY activity, further confirming that these proteins belong to the NusG-like (NusG SP ) family. Alignment of highly similar UpxYs led to the identification of a small region of these proteins predicted to confer specificity for their respective loci. Construction of an upaY-upeY hybrid that produced a protein in which a 17-amino-acid segment of UpaY was changed to that of UpeY altered UpaY's specificity, as it was now able to function in transcriptional antitermination of the PSE biosynthesis operon.

show abstract

Genetic Diversity of the Capsular Polysaccharide C Biosynthesis Region of Bacteroides fragilis

Cited by 2 publications

References 10 publications

Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases

Untangling the Role of Pathobionts from Bacteroides Species in Inflammatory Bowel Diseases

A Family of Transcriptional Antitermination Factors Necessary for Synthesis of the Capsular Polysaccharides of Bacteroides fragilis

Contact Info

Product

Resources

About