Bacteremia complicating gram-negative urinary tract infections: A population-based study

Al-Hasan, Majdi N.; Eckel‐Passow, Jeanette E.; Baddour, Larry M.

doi:10.1016/j.jinf.2010.01.007

Cited by 62 publications

(44 citation statements)

References 26 publications

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“…K. pneumoniae was the second most common isolate and P. mirabilis was the third most common, consistent with previous reports [23][24][25][26].…”

Section: Descriptive Statisticssupporting

confidence: 91%

“…The lower mortality rate in our study may be partially explained by a lower percentage of comorbidities such as dementia and a lower percentage of patients hospitalized for more than 21 days, which was found to be an important risk factor in one previous study; there was little difference in the definition of duration of hospitalization [5]. Lower mortality associated with community-acquired infection and E. coli UTI [24] may also partially explain these differences. In our study, the number of patients, which was not as high as in previous studies ([600 patients) may explain the similar detection rate of positive blood cultures between cases with two or more blood cultures and cases with one blood culture [11,12].…”

Section: Descriptive Statisticsmentioning

confidence: 41%

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Association between the number of blood cultures and appropriateness of care for suspected bacteremic urinary tract infection in the elderly

Hosaka

Bito

Matsubara

et al. 2011

Journal of Infection and Chemotherapy

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“…K. pneumoniae was the second most common isolate and P. mirabilis was the third most common, consistent with previous reports [23][24][25][26].…”

Section: Descriptive Statisticssupporting

confidence: 91%

Section: Descriptive Statisticsmentioning

confidence: 41%

Association between the number of blood cultures and appropriateness of care for suspected bacteremic urinary tract infection in the elderly

Hosaka

Bito

Matsubara

et al. 2011

Journal of Infection and Chemotherapy

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“…5 Bloodstream infections also are found frequently in patients with malignancies, 6 endocarditis, 7 and urinary tract infections. 8 In severe cases, bacteremia elicits a vigorous immune response that results in sepsis and septic shock. 9 Bloodstream infections often are accompanied by thrombocytopenia.…”

Section: Introductionmentioning

confidence: 99%

Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets

Kraemer

Campbell

Schwertz

et al. 2012

Blood

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Bacteria can enter the bloodstream in response to infectious insults. Bacteremia elicits several immune and clinical complications, including thrombocytopenia. A primary cause of thrombocytopenia is shortened survival of platelets. We demonstrate that pathogenic bacteria induce apoptotic events in platelets that include calpain-mediated degradation of Bcl-x L , an essential regulator of platelet survival. Specifically, bloodstream bacterial isolates from patients with sepsis induce lateral condensation of actin, impair mitochondrial membrane potential, and degrade Bcl-x L protein in platelets. Bcl-x L protein degradation is enhanced when platelets are exposed to pathogenic Escherichia coli that produce the poreforming toxin ␣-hemolysin, a response that is markedly attenuated when the gene is deleted from E coli. We also found that nonpathogenic E coli gain degrading activity when they are forced to express ␣-hemolysin. Like ␣-hemolysin, purified ␣-toxin readily degrades Bcl-x L protein in platelets, as do clinical Staphylococcus aureus isolates that produce ␣-toxin. Inhibition of calpain activity, but not the proteasome, rescues Bcl-x L protein degradation in platelets coincubated with pathogenic E coli including ␣-hemolysin producing strains. This is the first evidence that pathogenic bacteria can trigger activation of the platelet intrinsic apoptosis program and our results suggest a new mechanism by which bacterial pathogens might cause thrombocytopenia in patients with bloodstream infections. IntroductionBacteremia is a leading cause of morbidity and mortality in the United States and worldwide. 1,2 Risk factors for bacteremia include indwelling catheters, 3 trauma, 4 and surgery. 5 Bloodstream infections also are found frequently in patients with malignancies, 6 endocarditis, 7 and urinary tract infections. 8 In severe cases, bacteremia elicits a vigorous immune response that results in sepsis and septic shock. 9 Bloodstream infections often are accompanied by thrombocytopenia. 10 Adverse clinical outcomes commonly are observed in thrombocytopenic patients with documented bacteremia, and the severity of thrombocytopenia is associated with an increase in the rate of mortality of patients in the intensive care unit. 10,11 It generally is presumed that the infectious milieu induces thrombocytopenia by activating platelets that subsequently deposit in microvascular thrombi or get cleared from the circulation. 12 Indeed, bacteria or bacterial products can induce platelet activation by directly or indirectly binding to surface receptors such as integrin ␣ IIb ␤ 3 , GPIb, and TLRs. 13 However, the precise mechanisms that underpin bacteremia-induced thrombocytopenia remain poorly defined.In addition to the biochemical pathways that regulate classic platelet functional responses such as aggregation and adhesion, it has been demonstrated recently that megakaryocytes and platelets possess an intrinsic apoptosis program. 14,15 Key components of the platelet apoptotic pathway include the prosurvival protein Bcl-x L and...

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“…In addition, this protein contributes to disseminated infections (5,12), such as those that result from an ascending urinary tract infection (1,6,11). Indeed, it is estimated that Gram-negative bacilli, including E. coli, are the cause of up to 24% of cases of bacteremia annually in the United States alone (10).…”

mentioning

confidence: 99%

The Repeat-In-Toxin Family Member TosA Mediates Adherence of Uropathogenic Escherichia coli and Survival during Bacteremia

et al. 2012

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Uropathogenic Escherichia coli (UPEC) is responsible for the majority of uncomplicated urinary tract infections (UTI) and represents the most common bacterial infection in adults. UPEC utilizes a wide range of virulence factors to colonize the host, including the novel repeat-in-toxin (RTX) protein TosA, which is specifically expressed in the host urinary tract and contributes significantly to the virulence and survival of UPEC. tosA, found in strains within the B2 phylogenetic subgroup of E. coli, serves as a marker for strains that also contain a large number of well-characterized UPEC virulence factors. The presence of tosA in an E. coli isolate predicts successful colonization of the murine model of ascending UTI, regardless of the source of the isolate. Here, a detailed analysis of the function of tosA revealed that this gene is transcriptionally linked to genes encoding a conserved type 1 secretion system similar to other RTX family members. TosA localized to the cell surface and was found to mediate (i) adherence to host cells derived from the upper urinary tract and (ii) survival in disseminated infections and (iii) to enhance lethality during sepsis (as assessed in two different animal models of infection). An experimental vaccine, using purified TosA, protected vaccinated animals against urosepsis. From this work, it was concluded that TosA belongs to a novel group of RTX proteins that mediate adherence and host damage during UTI and urosepsis and could be a novel target for the development of therapeutics to treat ascending UTIs. R epeat-in-toxin (RTX) proteins are widespread among Gramnegative bacteria, with more than 1,000 family members detected in a survey of genome sequences from 251 bacterial species (21). Two common features present in known RTX family members are a characteristic glycine-and aspartate-rich repeat near the C terminus of the protein and a conserved type 1 secretion system (T1SS) that exports the protein into the extracellular environment, bypassing the periplasmic space (21, 37). The model protein for the RTX family, alpha-hemolysin, inserts into host membranes and forms pores that allow an influx of Ca 2ϩ into host cells, altering host physiology or leading to cell death (37). Additional RTX family members have displayed a wide array of functions in bacterial pathogens; secreted proteases (24, 29) and lipases (9, 40), cross-linkers of cellular actin that cause host cell rounding (28), and surface-associated coats of protein that form the bacterial S-layer (26, 30) represent a few examples of these diverse functions. However, most RTX family members remain uncharacterized. Given the widespread distribution and diverse roles that known family members contribute to bacterial pathogenesis, the identification and characterization of novel RTX family members remains an important area of research.One of the best characterized RTX family members, alphahemolysin, enhances host damage in the urinary tract during an Escherichia coli infection (32). In addition, this protein contributes to...

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Bacteremia complicating gram-negative urinary tract infections: A population-based study

Cited by 62 publications

References 26 publications

Association between the number of blood cultures and appropriateness of care for suspected bacteremic urinary tract infection in the elderly

Association between the number of blood cultures and appropriateness of care for suspected bacteremic urinary tract infection in the elderly

Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets

The Repeat-In-Toxin Family Member TosA Mediates Adherence of Uropathogenic Escherichia coli and Survival during Bacteremia

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