Freya Darling Eriksen (University Of Groningen)

Summary of presentation:
The rapid emergence of antibiotic-resistant bacteria poses a critical threat to global health. Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are highly recurrent, even after antibiotic treatment. We now know that urinary pathogens do not live alone, but instead live and interact with diverse taxa residing in the urobiome. To what extent these ecological interactions can change antibiotic susceptibility of uropathogens, is unknown. Here we investigated antibiotic susceptibility and de-novo resistance evolution in a polymicrobial UTI co-culture, exposing Escherichia coli and Enterococcus faecalis to the antibiotic fosfomycin during a 3-day Multispecies Adaptive Laboratory Evolution experiment. We found a significantly higher population size of E. faecalis in co-culture with E. coli, but only when exposed to fosfomycin. We also observed increased fosfomycin tolerance of E. faecalis in co-culture, even without prior exposure to the antibiotic. Untargeted mass spectrometry and computational metabolomics analysis revealed an extensive reorganization of the extracellular metabolic niche in co-culture with fosfomycin, distinct from E. coli monocultures, possibly through mechanisms such as cross-feeding, cofactor redistribution, and niche restructuring. These findings demonstrate that microbial interactions can shape antibiotic susceptibility of uropathogens to fosfomycin, and underscore the importance of adopting ecological perspectives in the development of future treatment strategies for complex microbial infections.