Distinct morphological fates of uropathogenic E. coli intracellular bacterial communities: dependency on urine composition and pH.

American Society for Microbiology
Publication Type:
Journal Article
Infection and immunity, 2020
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Infection and Immunity-2020-Iosifidis-IAI.00884-19.full.pdfAccepted version3.57 MB
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Uropathogenic E. coli (UPEC) is the leading cause of urinary tract infections (UTI). These bacteria undertake a multi-stage infection cycle involving invasion of and proliferation within urinary tract epithelial cells, leading to the rupture of the host cell and dispersal of the bacteria, some of which have a highly filamentous morphology. Here we established a microfluidics-based model of UPEC infection of immortalized human bladder epithelial cells that recapitulates the main stages of bacterial morphological changes during the acute infection cycle in vivo and allows the development and fate of individual cells to be monitored in real-time by fluorescence microscopy. The UPEC-infected bladder cells remained alive and mobile in non-confluent monolayers during the development of intracellular bacterial communities (IBCs). Switching from a flow of growth medium to human urine resulted in immobilization of both uninfected and infected bladder cells. IBCs continued to develop and then released many highly filamentous bacteria via an extrusion-like process, whereas others showed strong UPEC proliferation yet no detected filamentation. The filamentation response was dependent on the weak acidity of human urine and required component(s) in a low molecular-mass (<3000 Da) fraction from a mildly dehydrated donor. The developmental fate for bacteria therefore appears to be controlled by multiple factors that act at the level of the whole IBC, suggesting that variable local environments or stochastic differentiation pathways influence IBC developmental fates during infection.
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