<i>Escherichia coli</i>mediated urinary tract infections: Are there distinct uropathogenic<i>E. coli</i>(UPEC) pathotypes?

Marrs, Carl F.; Zhang, Lixin; Foxman, Betsy

doi:10.1016/j.femsle.2005.08.028

Cited by 188 publications

(172 citation statements)

References 47 publications

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“…Although Ͻ15% of all commensal E. coli isolates encode genes for HlyA expression, this value is substantially higher among strains that cause cystitis (31-48%), pyelonephritis (44 -49%), or bacteriaemia (39%) (Johnson, 1991;Marrs et al, 2002Marrs et al, , 2005. At high concentrations, HlyA is able to lyse erythrocytes and nucleated host cells, a process that may enable extraintestinal pathogens like UPEC to better cross mucosal barriers, damage effector immune cells, and gain enhanced access to host nutrients and iron stores (Cavalieri et al, 1984;Johnson, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…These data supported the possibility that a secreted factor, common to many UPEC isolates, negatively impacts Akt activation. Two secreted toxins often associated with UPEC strains are cytotoxic necrotizing factor 1 (CNF1) and HlyA (Marrs et al, 2005;Bonacorsi et al, 2006). Targeted disruption of each of these toxin-encoding genes in UTI89 revealed that hlyA, but not cnf1, was required for UTI89-mediated inactivation of Akt ( Figure 2B).…”

Section: Hlya Stimulates Akt Dephosphorylationmentioning

confidence: 99%

“…Strains of uropathogenic Escherichia coli (UPEC) are the leading cause of urinary tract infections (UTIs), which currently rank among the most common of infectious diseases worldwide (Foxman, 2003;Marrs et al, 2005). During the course of an infection, UPEC can stimulate a number of antimicrobial, proinflammatory, prodifferentiation, proliferation, and host cell death pathways (Mulvey, 2002;Mysorekar et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Inactivation of Host Akt/Protein Kinase B Signaling by Bacterial Pore-forming Toxins

Wiles

Dhakal

Eto

et al. 2008

MBoC

102

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Uropathogenic Escherichia coli (UPEC) are the major cause of urinary tract infections (UTIs), and they have the capacity to induce the death and exfoliation of target uroepithelial cells. This process can be facilitated by the pore-forming toxin ␣-hemolysin (HlyA), which is expressed and secreted by many UPEC isolates. Here, we demonstrate that HlyA can potently inhibit activation of Akt (protein kinase B), a key regulator of host cell survival, inflammatory responses, proliferation, and metabolism. HlyA ablates Akt activation via an extracellular calcium-dependent, potassium-independent process requiring HlyA insertion into the host plasma membrane and subsequent pore formation. Inhibitor studies indicate that Akt inactivation by HlyA involves aberrant stimulation of host protein phosphatases. We found that two other bacterial pore-forming toxins (aerolysin from Aeromonas species and ␣-toxin from Staphylococcus aureus) can also markedly attenuate Akt activation in a dose-dependent manner. These data suggest a novel mechanism by which sublytic concentrations of HlyA and other pore-forming toxins can modulate host cell survival and inflammatory pathways during the course of a bacterial infection. INTRODUCTIONStrains of uropathogenic Escherichia coli (UPEC) are the leading cause of urinary tract infections (UTIs), which currently rank among the most common of infectious diseases worldwide (Foxman, 2003;Marrs et al., 2005). During the course of an infection, UPEC can stimulate a number of antimicrobial, proinflammatory, prodifferentiation, proliferation, and host cell death pathways (Mulvey, 2002;Mysorekar et al., 2002). In some cases, UPEC can reportedly modulate these signaling events, causing attenuation of host inflammatory responses and potentiating host apoptotic cascades (Klumpp et al., 2001(Klumpp et al., , 2006Hunstad et al., 2005;Billips et al., 2007). These phenomena have been linked in part to the suppression of nuclear factor-B (NF B) activation and downstream signaling by unknown factors associated with UPEC (Klumpp et al., 2001;Hunstad et al., 2005). By hindering host cytokine expression and ensuing inflammatory responses, UPEC may be better able to establish itself and multiply within the cells and tissues of the urinary tract. At the same time, UPEC-induced death of bladder and renal epithelial cells can compromise mucosal barriers, and it may thereby facilitate bacterial dissemination and persistence within the urinary tract (Mulvey et al., 1998Chen et al., 2003a;Bower et al., 2005;Eto et al., 2006;Mansson et al., 2007b).A key regulator of host cell survival pathways is Akt (also known as protein kinase B, PKB; for recent reviews, see Fayard et al., 2005;Song et al., 2005;Manning and Cantley, 2007). This serine/threonine kinase is able to inhibit apoptosis, and it can help control cell cycle and metabolic pathways, endocytosis and vesicular trafficking, and host inflammatory responses, including the activation of NF B. Akt is activated downstream of phosphoinositide 3-kinase (PI3-kinase), which it...

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Section: Discussionmentioning

confidence: 99%

Section: Hlya Stimulates Akt Dephosphorylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inactivation of Host Akt/Protein Kinase B Signaling by Bacterial Pore-forming Toxins

Wiles

Dhakal

Eto

et al. 2008

MBoC

102

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“…However, some strains are pathogenic and cause a wide variety of different intestinal as well as extra-intestinal diseases (Marrs et al, 2005). Extra-intestinal pathogenic E. coli (ExPEC) isolates are a medically significant group of pathogens responsible for significant morbidity, mortality and cost to the healthcare system as a result of urinary tract infections (UTIs), diverse intra-abdominal infections, pneumonia, surgical-site infections, meningitis, osteomyelitis, skin and soft-tissue infections (SSTIs) and bacteraemia (Russo & Johnson, 2006).…”

Section: Introductionmentioning

confidence: 99%

Colicin insensitivity correlates with a higher prevalence of extraintestinal virulence factors among Escherichia coli isolates from skin and soft-tissue infections

Petkovšek

Žgur-Bertok

Erjavec

2012

Journal of Medical Microbiology

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Colicins are toxic proteins with a narrow killing spectrum that are produced by colicinogenic Escherichia coli strains. The aim of this study was to analyse systematically whether extraintestinal virulence potential is linked to colicin (in)sensitivity. In total, 102 well-characterized E. coli isolates from skin and soft-tissue infections (SSTIs) were exposed to 17 single-colicinproducing strains, and the correlation between insensitivity to colicin and phylogenetic group as well as the extra-intestinal virulence potential of the SSTI strains was examined. The results showed that SSTI strains belonging to the B2 phylogenetic group were statistically significantly associated with insensitivity to at least ten colicins, and several colicin insensitivities were correlated with virulence factors. As far as is known, this is the first study to report such correlations. INTRODUCTIONEscherichia coli is a diverse bacterial species found naturally in the intestinal tract of humans and many other animal species. However, some strains are pathogenic and cause a wide variety of different intestinal as well as extra-intestinal diseases (Marrs et al., 2005). Extra-intestinal pathogenic E. coli (ExPEC) isolates are a medically significant group of pathogens responsible for significant morbidity, mortality and cost to the healthcare system as a result of urinary tract infections (UTIs), diverse intra-abdominal infections, pneumonia, surgical-site infections, meningitis, osteomyelitis, skin and soft-tissue infections (SSTIs) and bacteraemia (Russo & Johnson, 2006). As the causative agent of~90 % of all UTIs among ambulatory female patients (Johnson & Stamm, 1989), it is not surprising that the UTI subgroup of ExPEC has been studied the most extensively. Among SSTIs, E. coli is the third most prevalent species isolated (Moet et al., 2007). Nevertheless, strains from these infections have not been characterized extensively. All ExPEC strains have a common phylogenetic background deriving typically from phylogenetic groups B2 and D, and share the same spectrum of virulence determinants (Russo & Johnson, 2000).Colicins are narrow-killing-spectrum bacteriocins produced by E. coli. Each colicin is unique in its characteristics (see Table 1 for some examples) and they do not share the same killing efficiencies (Feldgarden & Riley, 1998). Whilst it has been shown that colicins prevent the growth of intestinal and uropathogenic E. coli isolates Schamberger et al., 2004; Stahl et al., 2004), a high prevalence of insensitivities to colicins among microbial populations isolated from animals, humans and patients with UTIs has also been reported (Feldgarden & Riley, 1998;Rijavec, 2010;Riley & Gordon, 1992). To our knowledge, the correlation between colicin insensitivity and virulence potential has not yet been investigated. Therefore, the prevalence of colicin insensitivity among E. coli SSTI isolates with known virulence potential was determined systematically by exposing 102 strains to 17 different colicins. Furthermore, for the first time,...

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“…Los genes estudiados se encuentran asociados a cepas de E. coli responsable de infecciones extra-intestinales, considerando el origen de su aislamiento y fueron los siguientes: hly (α-hemolisina), iucC (aerobactina), afa (adhesina afimbrial), fimH (pili tipo 1), neuC (antígeno capsular K1), sfa/foc (pili tipo S y fimbrias tipo 1C), cnf1 (factor necrosante citotóxico), papC (pili tipo P) [23][24][25] , usp (proteína uropatógena específica) 26,27 e ibeA (factor de invasión del endotelio cerebral) 26,27 . Cada gen se estudió en las 146 cepas.…”

Section: Detección De Secuencias Específicas De Genes De Virulencia (Gv)unclassified

Análisis genético y propiedades virulentas de cepas de Escherichia coliaisladas desde infección vaginal

Lobos

Padilla

2013

Rev. chil. infectol.

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Escherichia colimediated urinary tract infections: Are there distinct uropathogenicE. coli(UPEC) pathotypes?

Cited by 188 publications

References 47 publications

Inactivation of Host Akt/Protein Kinase B Signaling by Bacterial Pore-forming Toxins

Inactivation of Host Akt/Protein Kinase B Signaling by Bacterial Pore-forming Toxins

Colicin insensitivity correlates with a higher prevalence of extraintestinal virulence factors among Escherichia coli isolates from skin and soft-tissue infections

Análisis genético y propiedades virulentas de cepas de Escherichia coliaisladas desde infección vaginal

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