Uropathogenic E. coli Niche-Occupancy Determines the Effects of Mucosal Vaccine Against FimH

In people with urinary tract infections (UTIs), uropathogenic E. coli (UPEC) frequently colonizes the gut where it forms a reservoir and contributes to recurrent UTI. Targeting UPEC within the gut using mucosal immunization is a potentially promising antibiotic-sparing strategy to prevent UTIs by depleting the reservoir. The mannose-binding FimH adhesin that tips type 1 pili is a critical virulence factor in UTI and aids in gut colonization. Here, we test the ability of a FimH mucosal vaccine to reduce gut colonization in mice. Our data show that the depletion of an introduced UPEC strain induced by FimH vaccination was influenced by microbial competition from other pre-established members of a diverse microbiota. This microbial competition partially restricted an incoming UPEC strain to the mucus, where immunization hindered UPEC colonization and was associated with reduced FimH-expression. Together, these data demonstrate that the effectiveness of an oral FimH vaccine relies on intra-niche competition, highlighting the complexity of host-pathogen interactions which need to be considered as we further hone our immune tools to target gut microbes.