PubMed · 3299643
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H R Ingham, P R Sisson. Microbial synergy.. https://doi.org/10.1093/clinids%2F9.3.659
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Symbiotic gut bacteria must re-establish themselves in every host generation, yet the molecular strategies enabling this inheritance remain poorly understood. Here, we show that Bacteroides fragilis uses a membrane glycolipid, alpha-galactosylceramide (BfaGC), to colonize the neonatal gut. Genome-wide fitness profiling revealed that BfaGC biosynthesis is selectively required during early life, when transient oxygenation creates a physiological bottleneck for strict anaerobes. Mechanistically, BfaGC reduces membrane proton permeability, sustaining the proton-motive force that supports aerobic respiration. This oxygen-responsive adaptation simultaneously generates a host-facing immunomodulatory signal that calibrates neonatal natural killer T (NKT) cell development, linking bacterial fitness to immune maturation through a single metabolite. The same mechanism also enables niche expansion by enterotoxigenic strains, revealing context-dependent consequences. Notably, this strategy is distinct among gut Bacteroidales: other prominent members synthesize a different sphingolipid subclass supporting broader fitness, implying divergent evolutionary strategies. Our findings provide time-resolved insight into how bacterial metabolites shape host-microbiota symbiosis across development.
Since other viruses can influence expression of human papillomavirus (HPV) 16 E6-E7 genes in vitro, this study addressed whether specific vaginal bacteria do so as well. The vaginal microflora of 18 women with cervical intraepithelial neoplasia (CIN) or normal histology and HPV 16 infection, was evaluated by quantitative culture. Expression of HPV 16 E6-E7 oncogenes was assessed in exfoliated cervical cells by quantitative polymerase chain reaction. HPV 16 expression was also quantitated in CaSki carcinoma cell line cocultured with Bacteroides fragilis or Lactobacillus acidophilus. Isolation of Lactobacillus sp. (p = 0.05) and expression of the E6*II transcript (p = 0.03) were associated with low-grade CIN or normal histology. However, changes in E6-E7 expression were not associated independently with isolation of a specific microorganism. Similarly, expression of HPV 16 E6-E7 oncogenes in vitro was unaltered in the presence of bacteria. These results suggest that vaginal microorganisms are unlikely to alter the natural history of HPV-associated CIN by influencing HPV oncogene expression.
Strains of Bacteroides fragilis associated with diarrheal disease (enterotoxigenic B. fragilis) produce a 20-kDa zinc-dependent metalloprotease toxin (B. fragilis enterotoxin; BFT) that reversibly stimulates chloride secretion and alters tight junctional function in polarized intestinal epithelial cells. BFT alters cellular morphology and physiology most potently and rapidly when placed on the basolateral membrane of epithelial cells, suggesting that the cellular substrate for BFT may be present on this membrane. Herein, we demonstrate that BFT specifically cleaves within 1 min the extracellular domain of the zonula adherens protein, E-cadherin. Cleavage of E-cadherin by BFT is ATP-independent and essential to the morphologic and physiologic activity of BFT. However, the morphologic changes occurring in response to BFT are dependent on target-cell ATP. E-cadherin is shown here to be a cellular substrate for a bacterial toxin and represents the identification of a mechanism of action, cell-surface proteolytic activity, for a bacterial toxin.