Early invasion of the bladder wall by solitary bacteria protects UPEC from antibiotics and neutrophil swarms in an organoid model

Kunal Sharma, Vivek V Thacker, Neeraj Dhar, Maria Clapés Cabrer, Anaëlle Dubois, François Signorino-Gelo, Jasper Mullenders, Graham W Knott, Hans Clevers, John D McKinney

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)109351
JournalCell Reports
Volume36
Issue number3
DOIs
Publication statusPublished - 20 Jul 2021

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