Intracellular Uropathogenic E. coli Exploits Host Rab35 for Iron Acquisition and Survival within Urinary Bladder Cells.

Citation data:

PLoS pathogens, ISSN: 1553-7374, Vol: 11, Issue: 8, Page: e1005083

Publication Year:
2015
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Repository URL:
https://scholarscompass.vcu.edu/micr_pubs/48; https://scholarscompass.vcu.edu/micr_pubs/39; https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1045&context=micr_pubs; https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1038&context=micr_pubs
PMID:
26248231
DOI:
10.1371/journal.ppat.1005083; 10.1371/journal.ppat.1005083.g007; 10.1371/journal.ppat.1005083.g001; 10.1371/journal.ppat.1005083.g006; 10.1371/journal.ppat.1005083.g005; 10.1371/journal.ppat.1005083.g002; 10.1371/journal.ppat.1005083.g003; 10.1371/journal.ppat.1005083.g004
PMCID:
4527590; PMC4527590
Author(s):
Neha Dikshit; Pradeep Bist; Shannon N. Fenlon; Niyas Kudukkil Pulloor; Christelle En Lin Chua; Marci A. Scidmore; Jason A. Carlyon; Bor Luen Tang; Swaine L. Chen; Bindu Sukumaran; Isabelle Derré Show More Hide
Publisher(s):
Public Library of Science (PLoS); Figshare
Tags:
Immunology and Microbiology; Biochemistry, Genetics and Molecular Biology; Biological Sciences; bladder epithelial cells; vivo murine model; support upec survival; bec; urinary bladder cells recurrent; coli exploits host rab 35; gtpase rab 35; degradative lysosomal fusion; novel survival mechanism; rab 35; intracellular upec; intracellular infection; ucv; cell culture model; uti; intracellular iron levels; intracellular upec infection; intracellular uropathogenic e; endosomal recycling; Medicine and Health Sciences
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article description
Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles (UCV) within BEC. Rab35 plays a role in endosomal recycling of transferrin receptor (TfR), the key protein responsible for transferrin-mediated cellular iron uptake. UPEC enhance the expression of both Rab35 and TfR and recruit these proteins to the UCV, thereby supplying UPEC with the essential nutrient iron. Accordingly, Rab35 or TfR depleted cells showed significantly lower intracellular iron levels and reduced ability to support UPEC survival. In the absence of Rab35, UPEC are preferentially trafficked to degradative lysosomes and killed. Furthermore, in an in vivo murine model of persistent intracellular infection, Rab35 also colocalizes with intracellular UPEC. We propose a model in which UPEC subverts two different vesicular trafficking pathways (endosomal recycling and degradative lysosomal fusion) by modulating Rab35, thereby simultaneously enhancing iron acquisition and avoiding lysosomal degradation of the UCV within bladder epithelial cells. Our findings reveal a novel survival mechanism of intracellular UPEC and suggest a potential avenue for therapeutic intervention against recurrent UTI.