Proteomic Adaptations of <i>Escherichia coli</i> in Urinary Tract Infection Patients

Urinary tract infections (UTIs) are among the most prevalent bacterial infections worldwide, with <i>Escherichia coli</i> responsible for the majority of cases. While much of what is known about <i>E. coli</i> physiology comes from laboratory culture, this paradigm overlooks the critical influence of the unique host environment on bacterial adaptation and pathogenesis. Here, we analyzed the <i>E. coli</i> proteome directly from the urine of five UTI-positive patients and compared it to their respective isolates after a single in vitro passage. The comparison revealed profound proteomic changes; notably, 37 proteins consistently expressed across all patient-derived samples were uniformly absent postculture. Functional analysis of the host-adapted <i>E. coli</i> proteome versus after a single laboratory passage (i.e., culture) points to key roles in nutrient acquisition, virulence, stress tolerance, and host interaction, highlighting adaptive features that are lost during culture. Among these were outer membrane transporters such as FepA, CirA, and YfiB, surface-exposed proteins with diagnostic and vaccine potential, and metabolic or stress-response enzymes such as SodA, NirB, MetE, and IlvA, which represent attractive drug targets due to their essential in vivo roles and absence in humans. Our findings demonstrate the value of profiling pathogens taken directly from the host environment, revealing proteins that may serve as novel biomarkers or therapeutic targets for UTIs.