T6SS mediated antagonism in the mammalian gut. A. Three
different Proteobacterial enteric pathogens, Vibrio cholerae,
Salmonella enterica Typhimurium, and Shigella
sonnei use T6SSs to target resident gut E. coli to
overcome colonization resistance and cause disease in animal models (33–37). In the case of V. cholerae, the lysed
E. coli initiate innate immune responses that upregulate
virulence factors and increase dissemination (33). B.
Bacteroides fragilis GA3 T6SS antagonize nearly all gut
Bacteroidales species in vitro. In vivo,
strong antagonistic effects are seen between two distinct B.
fragilis strains likely due to their localization at the mucosal
surface where they will make frequent contacts. This intraspecies antagonism may
lead to the dominance of one strain. B. vulgatus was also
significantly antagonized by a B. fragilis GA3 T6SS, possibly
due to overlapping nutritional niches. In contrast, a significant antagonistic
effect by the GA3 T6SS of B. fragilis was not observed when
co-inoculated with B. thetaiotaomicron. These varied effects
may be due to the substrate preferences of these species that may spatially
segregate them under normal dietary conditions.