Intramacrophage survival of uropathogenic Escherichia coli: Differences between diverse clinical isolates and between mouse and human macrophages
AuthorsBokil, Nilesh J.
Carey, Alison J.
Stacey, Katryn J.
Saunders, Bernadette M.
Ulett, Glen C.
Schembri, Mark A.
Sweet, Matthew J.
KAUST DepartmentApplied Mathematics and Computational Science Program
Biological and Environmental Sciences and Engineering (BESE) Division
Red Sea Research Center (RSRC)
Computational Bioscience Research Center (CBRC)
Integrative Systems Biology Lab
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AbstractUropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1 + vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival. © 2011 Elsevier GmbH.
SponsorsThis work was supported by project grants from the National Health and Medical Research Council of Australia (APP1005315, 631531 and 569674). KJS, MAS and MJS are supported by ARC Future Fellowships, and MJS is supported by an honorary NHMRC Senior Research Fellowship. Confocal microscopy was performed at the Australian Cancer Research Foundation (ACRF)/Institute for Molecular Bioscience Dynamic Imaging Facility for Cancer Biology, which was established with the support of the ACRF. We thank Prof. Scott Hultgren for providing strain UTI89.
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