Aryl polyenes expressed by Uropathogenic <i>Escherichia coli</i>contribute to pathogenesis in a mouse model with an aberrant macrophage polarization

Abstract Uropathogenic Escherichia coli (UPEC) is a causative agent of urinary tract infections (UTIs), and one the most common causes pyelonephritis. Interestingly, UPEC often found as non-pathobiont in gut flora. The transition from flora to pathogen for dependent upon flexible tropism, number virulence factors that aid UPEC’s colonization invasion tract. We recently demonstrated role E. aryl polyenes (APEs) potential fitness factor. current hypothesis APEs contribute host system. are encoded by biosynthetic gene cluster (BGC) family identified among many gram-negative bacteria. products this BGC lipids comprised an head group conjugated double bond system, which structurally reminiscent established gram-positives. In addition structural mimicry, APE expression conferred resistance reactive oxygen species enhanced biofilm formation. UTI mouse model, infection with constitutively expressed (UPEC APE+) increased pathogenicity. Transcriptomic analyses vitro co-incubation experiments indicates APE+exposure influences macrophage transcription profile differently compared WT. Taken together, our findings suggest aids bacterial immune modulation during infection. Therefore, targeting product may be viable therapeutic approach reduce pathogenic populations while leaving commensal microflora unharmed minimize tissue damage. NIAID RO1AI153173 Cleveland Clinic Foundation