Uropathogenic Escherichia coli niche occupancy determines the effects of mucosal vaccine against FimH

In people with urinary tract infections (UTIs), uropathogenic Escherichia coli (UPEC) often colonizes the gut, forming a reservoir and contributing to recurrent UTIs. Mucosal immunization targeting UPEC within the gut presents a promising antibiotic-sparing strategy to prevent UTIs by depleting this reservoir. The FimH adhesin that tips type 1 pili is a critical virulence factor in UTI and aids in gut colonization. Here, we assess the potential of a FimH mucosal vaccine to reduce UPEC gut colonization in mice. Our findings show that vaccine-induced depletion of an introduced UPEC strain was influenced by microbial competition from pre-established microbes. This competition partially restricted the incoming UPEC strain to the mucus, where immunization was associated with reduced FimH expression. These results demonstrate that oral FimH vaccine effectiveness relies on intra-niche competition, underscoring the complexity of host-pathogen interactions that must be considered as we refine immune tools to target gut microbes.