title: Intramacrophage survival of uropathogenic Escherichia coli: differences between diverse clinical isolates and between mouse and human macrophages.
abstract: Uropathogenic 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.
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, Qld 4072, Australia.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Bokil
authors.forename: Makrina
authors.initials: M
authors.lastname: Totsika
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Carey
authors.forename: Katryn J
authors.initials: KJ
authors.lastname: Stacey
authors.forename: Viktoria
authors.initials: V
authors.lastname: Hancock
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Saunders
authors.forename: Timothy
authors.initials: T
authors.lastname: Ravasi
authors.forename: Glen C
authors.initials: GC
authors.lastname: Ulett
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schembri
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sweet
mesh_terms: D000818:Animals; D003556:Cystitis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005260:Female; D058507:Host Specificity / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D001743:Urinary Bladder / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D019459:Urothelium / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014774:Virulence / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D037521:Virulence Factors