Credit: Nicola Hawes/Macmillan Publishers Limited

The bacterial species Bacteroides fragilis includes commensal strains and strains that are opportunistic human pathogens; enterotoxigenic B. fragilis (ETBF) strains express the colitis-inducing B. fragilis toxin (BFT). However, humans are also asymptomatically colonized by ETBF, which suggests that both microbial virulence factors and host susceptibility factors influence disease pathogenesis. In a recent study, Hecht et al. developed a mouse model of homeostatic ETBF colonization to investigate factors that contribute to disease susceptibility.

Colonic mucus maintains intestinal homeostasis by protecting the epithelium from enteric microorganisms and by providing a carbon source to promote the growth of commensals in this niche. Investigating the role of the secreted intestinal glycoprotein mucin 2 (MUC2) in ETBF pathogenesis, the authors showed that colonization of MUC2-deficient mice with ETBF was lethal. However, animals with intact colonic mucus that were colonized by ETBF, and MUC2-deficient mice that were colonized with ETBF strains that lack BFT, were unaffected.

Next, the authors showed that a two-component response regulator system, comprising RprY and RprX, regulates the expression of bft. They detected decreased bft transcript levels when mice were inoculated with an ETBF strain that overexpressed RprX, whereas bft transcript levels were increased when the authors used a mutant bacterial strain that lacked RprX. Finally, colonization of MUC2-deficient mice with bacteria that overexpressed RprY or RprX prevented lethal disease.

the findings link the host environment to pathogen virulence

In summary, this study reveals a two-component response regulator system that regulates the expression of BFT, and the findings link the host environment to pathogen virulence.