Disruption of Genes Encoding Putative Zwitterionic Capsular Polysaccharides of Diverse Intestinal Bacteroides Reduces the Induction of Host Anti-Inflammatory Factors

Abstract

Bacterial zwitterionic capsular polysaccharides (ZPS), such as polysaccharide A (PSA) of the intestinal commensal Bacteroides fragilis, have been shown to modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). We previously used a genomic screen to identify diverse host-associated bacteria with the predicted genetic capacity to produce ZPSs related to PSA of B. fragilis and hypothesized that genetic disruption (KO) of a key functional gene within these operons would reduce the anti-inflammatory activity of these bacteria. We found that ZPS-KO bacteria in two common gut commensals, Bacteroides uniformis and Bacteroides cellulosilyticus, had a reduced ability to induce Tregs and IL-10 in stimulations of human peripheral blood mononuclear cells (PBMCs). Additionally, we found that macrophage stimulated with either wildtype B. fragilis or B. uniformis produced significantly more IL-10 than KOs, indicating a potentially novel function of ZPS of shifting the cytokine response in macrophages to a more anti-inflammatory state. These findings support the hypothesis that these related ZPS may represent a shared strategy to modulate host immune responses.

The Mechanism of Elizabethkingia miricola Infection of the Black Spotted Frog as Revealed by Multi-Omics Analysis

“…As intestinal commensals and symbiotic organisms, it was hypothesized that the reduction in Bacteroidota prevalence may be associated with E. miricola infection in this study. Currently, there is conclusive evidence demonstrating that Bacteroidota, via their metabolites (e.g., podocarp polysaccharide A), can inhibit bacterial and viral infections whilst also modulating host immune response strategies [47,48].…”

The role of the glycome in symbiotic host-microbe interactions

“…Still, in further studies of PSA effects on antigen presenting cells a significant polarisation towards anti-inflammatory macrophages has been demonstrated ( Zhou et al 2022 ). Moreover, inactivation of PSA reduces the induction of host anti-inflammatory factors ( Arnolds et al 2023 ). On a broader scale, a bioinformatic inspection of publicly available genomic sequences for the presence of PSA homologues revealed its wide occurrence in taxonomically diverse bacteria that included Bacteroidales, Erysipelotrichales, Clostridiales, and Bacillales orders ( Neff et al 2016 ).…”