Binding to and killing of human renal epithelial cells by hemolytic P-fimbriated E. coli

Trifillis, Anna L.; Donnenberg, Michael S.; Cui, Xiaoling; Russell, Robert G.; Sj, Utsalo; Mobley, Harry L. T.; Warren, John W.

doi:10.1038/ki.1994.370

Cited by 54 publications

(41 citation statements)

References 19 publications

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“…Capsular antigen K1 is known to play a key role in E. coli survival in blood, as it is a major determinant of serum resistance (16,17). Likewise, hemolysin is involved in the extraintestinal virulence of E. coli (24) and may damage human renal epithelial cells, facilitating passage of bacteria through the epithelial barrier (13,23). However, among our 61 strains harboring K1 and/or hemolysin, only 7 (10%) harbored both factors (not shown).…”

mentioning

confidence: 87%

Comparative Prevalence of Virulence Factors in Escherichia coli Causing Urinary Tract Infection in Male Infants with and without Bacteremia

et al. 2006

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Escherichia coli isolates causing urinary tract infection in 83 male infants younger than 90 days with and without bacteremia were compared for phylogenetic groups and the presence of 10 virulence factors. Our result suggest that the absence of both hemolysin and antigen K1 may be used as a negative predictive factor for bacteremia.Urinary tract infection (UTI) is the major cause of bacterial infection in infants younger than 90 days. The estimated incidence of UTI in this age group is about 1% (22), and UTI is responsible for up to 10% of cases of fever (6,14). UTI shows a marked male predominance during this period of age, and bacteremia occurs in one-quarter of cases, compared to less than 5% in older subjects (1,7,25). Although the proclivity for bloodstream infection in the very young is known, the mechanisms underlying the negative correlation between bacteremia and age in this setting are unknown. The decision to treat young infants with UTI with parenteral versus oral antibiotics is in part based on the risk of bacteremia. Indeed, the main complication of urosepsis in this young population is meningitis, which occurs in about 10% of bacteremic patients (1). However, the sensitivity of blood culture is low in this age group, mainly because only one sample of limited volume can be drawn each day. In addition, one-third of young infants with bacteremia have fewer than one pathogen per milliliter of blood (15). Several teams have attempted to identify factors that may be used to distinguish pediatric patients with and without bacteremia, in terms of clinical, biological, or radiological features and outcome (1,8,9,21). The only significant difference so far identified is that patients with bacteremia are more likely to have anatomical or functional urinary tract disorders (1, 9).Escherichia coli is the leading cause of bacterial UTI. Knowledge of the molecular pathogenicity of extraintestinal E. coli infections has improved markedly over the last decade (11). However, the possible relationship between the virulence genotype of infecting E. coli strains and the risk of bacteremia has not yet been studied in young infants with UTI. Here, we compared two collections of E. coli isolated from infants with bacteremic and nonbacteremic UTI, focusing on phenotypic and genetic determinants that might serve to predict bacteremia and to guide treatment.To constitute the cohort of patients with bacteremia, we reviewed the records of all infants younger than 90 days hospitalized in our institution with community-acquired E. coli urosepsis between January 1992 and December 2002. The inclusion criteria were blood culture yielding E. coli and Ն10 5CFU of E. coli per ml in a urine bag sample with at least 10 white blood cells per mm 3 . The patients without bacteremia were a part of a cohort described elsewhere (4). As UTI at this age affects mainly boys and in order to rule out confounding factors such as gender and urinary tract abnormalities, only isolates from boys with normal voiding cystourethrography or minor vesicour...

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confidence: 87%

Comparative Prevalence of Virulence Factors in Escherichia coli Causing Urinary Tract Infection in Male Infants with and without Bacteremia

et al. 2006

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“…Heparinized blood (5 mL) collected from the jugular vein of adult male rats was carefully layered over 5 mL of Ficoll-Urografin (density of 1.077 g/cm 3 ) and centrifuged for 30 min at 200 × g. This procedure results in erythrocyte pelleting while the mononuclear fraction of leukocytes forms an interphase ring on the Ficoll surface, which was carefully collected. Leukocytes were transferred into another tube and centrifuged for 3 min at 200 × g. The resultant pellet was resuspended in 5 mL of DMEM/F12.…”

Section: Methodsmentioning

confidence: 99%

“…The uropathogen most frequently associated with this disease is the pyelonephritogenic subset of Escherichia coli, which is responsible for up to 85% of both complicated and uncomplicated UTIs (2). This disease is frequently accompanied by bacterial invasion and stimulation of acute inflammatory response (3,4). Toxin-induced epithelial damage and bladder hemorrhage contribute further to the pathogenicity of uropathogens in the kidney, with progression leading to renal damage including renal scarring and in extreme cases septicemia (5,6).…”

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confidence: 99%

Protective effect of mitochondria-targeted antioxidants in an acute bacterial infection

Plotnikov

Morosanova

Pevzner

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Acute pyelonephritis is a potentially life-threatening infection of the upper urinary tract. Inflammatory response and the accompanying oxidative stress can contribute to kidney tissue damage, resulting in infection-induced intoxication that can become fatal in the absence of antibiotic therapy. Here, we show that pyelonephritis was associated with oxidative stress and renal cell death. Oxidative stress observed in pyelonephritic kidney was accompanied by a reduced level of mitochondrial B-cell lymphoma 2 (Bcl-2). Importantly, renal cell death and animal mortality were both alleviated by mitochondria-targeted antioxidant 10(6′-plastoquinonyl) decylrhodamine 19 (SkQR1). These findings suggest that pyelonephritis can be treated by reducing mitochondrial reactive oxygen species and thus by protecting mitochondrial integrity and lowering kidney damage.inflammation | phenoptosis | urological diseases | innate immunity | toll-like receptors

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“…While ⌬hlyA mutants of UPEC are attenuated in animal models of infection outside the urinary tract, notably in several bacteremia models (7,40), no defect in colonization of bladder or kidney tissue was observed in a similar murine UTI model (35). Both in the urinary tract and during in vitro assays, alpha-hemolysin mediates damage to host cells (35,37) but is not necessary for successful colonization of the host urinary tract. Additional studies will be necessary to elucidate the function of tosA, but the results of this study implicate a different and important role for this novel RTX family member during a UTI mediated by E. coli.…”

Section: Vol 79 2011 Identification Of Upec Antigens Induced Duringmentioning

confidence: 99%

Identification of In Vivo -Induced Antigens Including an RTX Family Exoprotein Required for Uropathogenic Escherichia coli Virulence

2011

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Uncomplicated urinary tract infections (UTI) are caused most commonly by uropathogenic Escherichia coli (UPEC). Whole-genome screening approaches, including transcriptomic, proteomic, and signature-tagged mutagenesis, have shown that UPEC highly expresses or requires genes for translational machinery, capsule, lipopolysaccharide, type 1 fimbriae, and iron acquisition systems during UTI. To identify additional genes expressed by UPEC during UTI, an immunoscreening approach termed in vivo-induced antigen technology (IVIAT) was employed to identify antigens produced during experimental infection that are not produced during in vitro culture. An inducible protein expression library, constructed from genomic DNA isolated from UPEC strain CFT073, was screened using exhaustively adsorbed pooled sera from 20 chronically infected female CBA/J mice. Using this approach, we identified 93 antigens induced by UPEC in vivo. A representative subset of these genes was tested by quantitative PCR for expression by CFT073 in vivo and during growth in human urine or LB medium in vitro; proWX, narJI, lolA, lolD, tosA (upxA), c2432, katG, ydhX, kpsS, and yddQ were poorly expressed in vitro but highly expressed in vivo. Of these, tosA, a gene encoding a predicted repeat-in-toxin family member, was expressed exclusively during UTI. Deletion of tosA in UPEC strain CFT073 resulted in significant attenuation in bladder and kidney infections during ascending UTI. By screening for in vivo-induced antigens, we identified a novel UPEC virulence factor and additional proteins that could be useful as potential vaccine targets.

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Binding to and killing of human renal epithelial cells by hemolytic P-fimbriated E. coli

Cited by 54 publications

References 19 publications

Comparative Prevalence of Virulence Factors in Escherichia coli Causing Urinary Tract Infection in Male Infants with and without Bacteremia

Comparative Prevalence of Virulence Factors in Escherichia coli Causing Urinary Tract Infection in Male Infants with and without Bacteremia

Protective effect of mitochondria-targeted antioxidants in an acute bacterial infection

Identification of In Vivo -Induced Antigens Including an RTX Family Exoprotein Required for Uropathogenic Escherichia coli Virulence

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