From ecology to evolution: the influence of microbial communities on uropathogen fitness and antibiotic resistance

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, with uropathogenic Escherichia coli being a primary causative agent. The urinary environment presents unique challenges for bacterial survival, and interactions within microbial communities can significantly affect bacterial growth, virulence, and antibiotic resistance evolution. This thesis aims to address the knowledge gaps in understanding how interactions between uropathogens and urinary microbiome bacteria influence their growth, fitness, and the evolution of antibiotic resistance in urine-like environments. I employed a combination of in vitro experiments, serial transfer assays, and long-term evolution experiments to investigate pairwise and higher-order interactions between bacterial species, as well as the impact of environmental spatial structure and microbial community context on antibiotic resistance evolution. The findings reveal that bacterial interactions in urine-like environments are predominantly negative, with inhibitory effects on population size, growth rate, and lag phase. Higher-order interactions lead to non-additive and often stronger inhibition of bacterial growth rates than predicted from pairwise interactions alone. The ecological context significantly affects the speed and ultimate level of antibiotic resistance evolution, with microbial interactions promoting the diversification of resistance evolution. Environmental structure and microbial community composition profoundly influence the path and outcome of antibiotic resistance evolution. This thesis challenges the outdated view of the urinary tract as a sterile environment and underscores the importance of considering the entire urinary microbiome in UTI research and treatment.

Dissertation: https://hdl.handle.net/11370/488a9430-3d11-4890-a6bc-d8c809856c45