Complement Protective Epitopes and CD55–Microtubule Complexes Facilitate the Invasion and Intracellular Persistence of Uropathogenic Escherichia coli

Rana, Tanu; Hasan, Rafia; Nowicki, Stella; Venkatarajan, Mathura S.; Singh, Rajbir; Urvil, Petri; Popov, Vsevolod L.; Braun, Werner; Popik, Waldemar; Goodwin, J. Shawn; Nowicki, B.

doi:10.1093/infdis/jit619

Cited by 13 publications

(16 citation statements)

References 36 publications

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“…6A and Fig. 6B, binding and uptake of bacteria coated bioparticles began after 10-15 min of incubation, as previously reported (Rana et al, 2014). While untreated cells exhibited a basal level phagocytosis, in cells treated with MCSF, there was a significant increase in S. aureus uptake.…”

Section: Resultssupporting

confidence: 87%

Validation of research trajectory 1 of an Exposome framework: Exposure to benzo(a)pyrene confers enhanced susceptibility to bacterial infection

Clark

Pellom

Booker

et al. 2016

Environmental Research

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The exposome provides a framework for understanding elucidation of an uncharacterized molecular mechanism conferring enhanced susceptibility of macrophage membranes to bacterial infection after exposure to the environmental contaminant benzo(a)pyrene, [B(a)P]. The fundamental requirement in activation of macrophage effector functions is the binding of immunoglobulins to Fc receptors. FcγRIIa (CD32a), a member of the Fc family of immunoreceptors with low affinity for immunoglobulin G, has been reported to bind preferentially to IgG within lipid rafts. Previous research suggested that exposure to B(a)P suppressed macrophage effector functions but the molecular mechanisms remained elusive. The goal of this study was to elucidate the mechanism(s) of B(a)P-exposure induced suppression of macrophage function by examining the resultant effects of exposure-induced insult on CD32-lipid raft interactions in the regulation of IgG binding to CD32. The results demonstrate that exposure of macrophages to B(a)P alters their lipid raft integrity by decreasing membrane cholesterol 25% while increasing CD32 into non-lipid raft fractions. This robust diminution in membrane cholesterol and 30% exclusion of CD32 from lipid rafts causes a significant reduction in CD32-mediated IgG binding to suppress essential macrophage effector functions. Such exposures across the lifespan would have the potential to induce an immunosuppressive endophenotypes in vulnerable populations.

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Section: Resultssupporting

confidence: 87%

Validation of research trajectory 1 of an Exposome framework: Exposure to benzo(a)pyrene confers enhanced susceptibility to bacterial infection

Clark

Pellom

Booker

et al. 2016

Environmental Research

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“…We demonstrated a role for Afa (but not type 1 fimbriae) in the adhesion of E. coli VR50 to T24 bladder epithelial cells. Afa has been shown to mediate adherence and invasion of E. coli in HeLa and Chinese hamster ovary cells (82,83). In the case of VR50, we previously reported that the strain does not readily invade T24 cells, with low numbers observed intracellularly (84).…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

et al. 2015

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e Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder. U rinary tract infections (UTIs) are among the most common infectious diseases of humans and a major cause of morbidity. It is estimated that 40 to 50% of all adult women experience at least one UTI episode in their lifetime (1). In addition to welldocumented symptomatic infections, many UTIs are asymptomatic. These infections, referred to as asymptomatic bacteriuria (ABU), represent a carrier state that resembles commensalism and occur in a percentage of the population, depending on age and gender. ABU patients may carry Ͼ10 5 CFU of a single bacterial strain/ml of urine for months or years without significant symptoms.Escherichia coli causes more than 80% of all symptomatic and asymptomatic UTIs. In general, strains that cause symptomatic UTI are collectively described as uropathogenic E. coli (UPEC), while strains that cause asymptomatic UTI are referred to as ABU E. coli. Both UPEC and ABU E. coli strains exhibit a high degree of genetic diversity that is largely attributed to the presence of virulence/fitness genes on mobile genetic elements referred to as pathogenicity islands (PAIs) or genomic islands (GIs) (2, 3). While no single virulence factor is uniquely definitive for UPEC or ABU E. coli, the ability to colonize the urinary tract is enhanced by a number of factors, including fimbriae (e.g., type 1, P, F1C, and Afa), autotransporter proteins (e.g., Ag43, UpaB, and UpaH), cell surface polysaccharides (e.g., O antigen), and siderophores (e.g., ente...

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“…In addition to adhesion, UPEC are also able to invade a number of host cell types. Once internalized in the host urothelial cells, UPEC are trafficked into late endosomal compartments forming reservoirs that allow the intracellular persistence of bacteria (Mulvey et al, 2001;Eto et al, 2006;Mysorekar & Hultgren, 2006;Rana et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Identification of antigen Ag43 in uropathogenic Escherichia coli Dr+ strains and defining its role in the pathogenesis of urinary tract infections

̨tek

Olszewski

et al. 2015

Microbiology

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Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are amongst the most common bacterial infectious diseases in the developed world. The urovirulence of UPEC is mainly associated with the surface-exposed fimbrial adhesins and adhesins of the autotransporter (AT) family. The best studied of these proteins is antigen Ag43 mediating cell aggregation, adhesion and biofilm development as the causes of chronic UTIs. The E. coli IH11128 Dr + (dra + ) strain of the Dr/Afa + family of adhesins possesses two major surfaceexposed virulence factors: Dr fimbrial polyadhesin and DraD protein (fimbrial tip subunit or protein component of the adhesive sheath). Here, we identified for the first time, to our knowledge, the agn43 gene encoding Ag43 in the WT clinical isolate of UPEC Dr + as a new virulence factor not yet tested. We also found that Dr fimbrial expression, which like Ag43 is under the control of a phase-variable mechanism, did not exclude Ag43 surface presentation. However, the presence of Dr fimbriae supported by other structures on the cell surface caused a physical neutralization of Ag43-mediated autoaggregation during in vitro growth. The fimbrial bundling further increased the distance between the adjacent Ag43 + cells, thus preventing head-to-tail association between surface-exposed Ag43 subunits and their interactions with the host cells. The investigations showed that Ag43 did not act as a specific adhesin and invasin, conversely to the major virulence factors of E. coli Dr + , but played significant roles in the viability and metabolic activity of bacterial cells forming biofilm, and in the survival of bacteria within invaded epithelial cells.

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Complement Protective Epitopes and CD55–Microtubule Complexes Facilitate the Invasion and Intracellular Persistence of Uropathogenic Escherichia coli

Abstract: E. coli target complement-protective CD55 epitopes for invasion and exploit CD55-MT complexes to escape phagolysosomal fusion, leading to a nondestructive parasitism that allows bacteria to persist intracellularly.

Cited by 13 publications

References 36 publications

Validation of research trajectory 1 of an Exposome framework: Exposure to benzo(a)pyrene confers enhanced susceptibility to bacterial infection

Validation of research trajectory 1 of an Exposome framework: Exposure to benzo(a)pyrene confers enhanced susceptibility to bacterial infection

Molecular Analysis of Asymptomatic Bacteriuria Escherichia coli Strain VR50 Reveals Adaptation to the Urinary Tract by Gene Acquisition

Identification of antigen Ag43 in uropathogenic Escherichia coli Dr+ strains and defining its role in the pathogenesis of urinary tract infections

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