Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli.
Strains of uropathogenic Escherichia coli (UPEC) can invade terminally differentiated superficial bladder epithelial cells and subsequently multiply, forming large biofilm-like inclusions referred to as pods. In contrast, within immature bladder cells UPEC enter a more quiescent state and often fail to replicate appreciably. As immature bladder epithelial cells undergo terminal differentiation the actin cytoskeleton is radically diminished, a phenomenon that we reasoned could influence the intracellular fate of UPEC. Here we show that UPEC within undifferentiated bladder cells is trafficked into acidic compartments having key features of late endosomes and lysosomes. These UPEC-containing vacuoles are often enmeshed within a network of actin filaments, the disruption of which stimulates intravacuolar growth and efflux of UPEC in cell culture-based studies. In this in vitro model system, release of UPEC into the host cytosol further stimulates intracellular bacterial growth and the rapid development of pod-like inclusions. These inclusions, as well as those observed using an in vivo mouse model, develop in association with cytokeratin intermediate filaments that may act as scaffolding for intracellular biofilm formation. Our data suggest an aetiological basis for recurrent urinary tract infections, linking bladder cell differentiation and the accompanying redistribution of actin microfilaments with the resurgence of UPEC from quiescent intravacuolar reservoirs within the bladder epithelium.
Eto
Danelle S
DS
Pathology Department, Division of Cell Biology and Immunology, University of Utah, Salt Lake City, UT 84112-0565, USA.
Sundsbak
Jamie L
JL
Mulvey
Matthew A
MA
D000199:Actins / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000502:physiology*; D004927:Escherichia coli Infections / Q000382:microbiology*; D005260:Female; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000378:metabolism / Q000382:microbiology*; D014552:Urinary Tract Infections / Q000382:microbiology*; D019459:Urothelium / Q000378:metabolism / Q000382:microbiology; D052118:Lysosomal-Associated Membrane Protein 1
D000199:Actins; D051907:Lysosomal Membrane Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1