1. Early invasion of the bladder wall by solitary bacteria protects UPEC from antibiotics and neutrophil swarms in an organoid model.
- Author
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Sharma K, Thacker VV, Dhar N, Clapés Cabrer M, Dubois A, Signorino-Gelo F, Mullenders J, Knott GW, Clevers H, and McKinney JD
- Subjects
- Animals, Cell Differentiation drug effects, Escherichia coli Infections microbiology, Escherichia coli Infections pathology, Female, Humans, Imaging, Three-Dimensional, Mice, Inbred C57BL, Microbial Viability drug effects, Movement, Neutrophils drug effects, Organoids drug effects, Organoids ultrastructure, Urinary Bladder pathology, Uropathogenic Escherichia coli drug effects, Uropathogenic Escherichia coli growth & development, Uropathogenic Escherichia coli ultrastructure, Mice, Anti-Bacterial Agents pharmacology, Models, Biological, Neutrophils pathology, Organoids microbiology, Urinary Bladder microbiology, Uropathogenic Escherichia coli physiology
- Abstract
Recurrence of uropathogenic Escherichia coli (UPEC) infections has been attributed to reactivation of quiescent intracellular reservoirs (QIRs) in deep layers of the bladder wall. QIRs are thought to arise late during infection following dispersal of bacteria from intracellular bacterial communities (IBCs) in superficial umbrella cells. Here, we track the formation of QIR-like bacteria in a bladder organoid model that recapitulates the stratified uroepithelium within a volume suitable for high-resolution live-cell imaging. Bacteria injected into the organoid lumen enter umbrella-like cells and proliferate to form IBC-like bodies. In parallel, single bacteria penetrate deeper layers of the organoid wall, where they localize within or between uroepithelial cells. These "solitary" bacteria evade killing by antibiotics and neutrophils and are morphologically distinct from bacteria in IBCs. We conclude that bacteria with QIR-like properties may arise at early stages of infection, independent of IBC formation and rupture., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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