A non-canonical autophagy-dependent role of the ATG16L1^T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence.

ABSTRACT: 50% of Caucasians carry a Thr300Ala variant (T300A) in the protein encoded by the macroautophagy/autophagy gene ATG16L1. Here, we show that the T300A variant confers protection against urinary tract infections (UTIs), the most common infectious disease in women. Using knockin mice carrying the human T300A variant, we show that the variant limits the UTI-causing bacteria, uropathogenic Escherichia coli (UPEC), from establishing persistent intracellular reservoirs, which can seed UTI recurrence. This phenotype is recapitulated in mice lacking Atg16l1 or Atg7 exclusively in the urothelium. We further show that mice with the T300A variant exhibit urothelial cellular abnormalities, including vesicular congestion and aberrant accumulation of UPK (uroplakin) proteins. Importantly, presence of the

SUBMITTER: Wang C 

PROVIDER: S-EPMC6351132 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature