A multinucleating Escherichia coli cytotoxin perturbs cell cycle in cultured epithelial cells

Miraglia, Alessandro Giamboi; Travaglione, Sara; Filippini, Perla; Fabbri, Alessia; Fiorentini, Carla; Falzano, Loredana

doi:10.1016/j.tiv.2006.08.013

Cited by 15 publications

(15 citation statements)

References 19 publications

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“…Cyclin B1 is essentially found in the cytoplasm region through the G2 phase until it translocates into the nucleus, which precedes the nuclear envelope breakdown (Falzano et al, 2006). It was demonstrated that CNF-1 reduces cyclin B1 expression and induces a sequestration of cyclin B1 in the cytoplasm that results in CDK1 inhibition and G2/M phase arrest (Falzano et al, 2006; Giamboi-Miraglia et al, 2007). …”

Section: Bacterial Cyclomodulinsmentioning

confidence: 99%

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Filho

Nicolas

Castro

et al. 2017

Front. Cell. Infect. Microbiol.

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Some bacterial pathogens modulate signaling pathways of eukaryotic cells in order to subvert the host response for their own benefit, leading to successful colonization and invasion. Pathogenic bacteria produce multiple compounds that generate favorable conditions to their survival and growth during infection in eukaryotic hosts. Many bacterial toxins can alter the cell cycle progression of host cells, impairing essential cellular functions and impeding host cell division. This review summarizes current knowledge regarding cyclomodulins, a heterogeneous family of bacterial effectors that induce eukaryotic cell cycle alterations. We discuss the mechanisms of actions of cyclomodulins according to their biochemical properties, providing examples of various cyclomodulins such as cycle inhibiting factor, γ-glutamyltranspeptidase, cytolethal distending toxins, shiga toxin, subtilase toxin, anthrax toxin, cholera toxin, adenylate cyclase toxins, vacuolating cytotoxin, cytotoxic necrotizing factor, Panton-Valentine leukocidin, phenol soluble modulins, and mycolactone. Special attention is paid to the benefit provided by cyclomodulins to bacteria during colonization of the host.

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Section: Bacterial Cyclomodulinsmentioning

confidence: 99%

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Filho

Nicolas

Castro

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Control and treated cells were fixed and processed as previously described (Giamboi-Miraglia et al, 2007). The following antibodies were used: anti-β-catenin and anti-E-cadherin antibodies (1:100, Santa Cruz Biotechnology) followed by the appropriate FITC-or TRITC-conjugated secondary antibody (Sigma-Aldrich).…”

Section: Immunofluorescence and Confocal Microscopymentioning

confidence: 99%

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 induces epithelial mesenchymal transition

Fabbri

Travaglione

Rosadi

et al. 2019

Cellular Microbiology

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Some toxigenic bacteria produce protein toxins with carcinogenic signatures, which either directly damage DNA or stimulate signalling pathways related to cancer. So far, however, only a few of them have been proved to favour the induction or progression of cancer. In this work, we report that the Rho-activating Escherichia coli protein toxin, cytotoxic necrotising factor 1 (CNF1), induces epithelial to mesenchymal transition (EMT) in intestinal epithelial cells. EMT is a crucial step in malignant tumour conversion and invasiveness. In the case of CNF1, it occurs by up-regulation of the transcription factors ZEB1 and Snail1, delocalisation of E-cadherin and β-catenin, activation of the serine/threonine kinase mTOR, accelerated wound healing, and invasion. However, our results highlight that nontransformed epithelial cells entail the presence of inflammatory factors, in addition to CNF1, to acquire a mesenchymal-like behaviour. All this suggests that the surrounding microenvironment, as well as the cell type, dramatically influences the CNF1 ability to promote carcinogenic traits.

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“…These deamidation reactions cause constitutive activation of RhoA, Rac, and Cdc42 (i.e., they maintain these GTPases in the GTP-bound state), which in turn triggers a myriad of effects on the target cell. Specifically, activation of RhoA, Rac, and/or Cdc42 can evoke actin cytoskeleton rearrangements (27,28,50,52,53), cell cycle abnormalities (14,21,24), and alterations in host cell gene signaling pathways that involve certain nuclear transcription factors (39, 48). Of relevance to this study, we…”

mentioning

confidence: 99%

Hemolysin of Uropathogenic Escherichia coli Evokes Extensive Shedding of the Uroepithelium and Hemorrhage in Bladder Tissue within the First 24 Hours after Intraurethral Inoculation of Mice

Smith¹,

Rasmussen²,

Grande³

et al. 2008

Infect Immun

133

106

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Many uropathogenic Escherichia coli (UPEC) strains produce both hemolysin (Hly) and cytotoxic necrotizing factor type 1 (CNF1), and the loci for these toxins are often linked. The conclusion that Hly and CNF1 contribute to urovirulence is supported by the results of epidemiological studies associating the severity of urinary tract infections (UTIs) with toxin production by UPEC isolates. Additionally, we previously reported that mouse bladders and rat prostates infected with UPEC strain CP9 exhibit a more profound inflammatory response than the organs from animals challenged with CP9cnf 1 and that CNF1 decreases the antimicrobial activities of polymorphonuclear leukocytes. More recently, we created an Hly mutant, CP9⌬hlyA 1 ::cat, and showed that it was less hemolytic and destructive for cultured bladder cells than CP9 was. Here we evaluated the relative effects of mutations in hlyA 1 or cnf 1 alone or together on the pathogenicity of CP9 in a mouse model of ascending UTI. To do this, we constructed an hlyA 1 -complemented clone of CP9⌬hlyA 1 ::cat and an hlyA 1 cnf 1 CP9 double mutant. We found that Hly had no influence on bacterial colonization of the bladder or kidneys in single or mixed infections with the wild type and CP9⌬hlyA 1 ::cat but that it did provoke sloughing of the uroepithelium and bladder hemorrhage within the first 24 h after challenge. Finally, we confirmed that CNF1 expression induces bladder inflammation and, in particular, as shown in this study, submucosal edema. From these data, we speculate that Hly and CNF1 may be largely responsible for the signs and symptoms of cystitis in humans infected with toxigenic UPEC.Urinary tract infections (UTIs) include infections of the bladder (cystitis) and/or kidney (pyelonephritis) and account for more than 7 million office visits each year by otherwise healthy women (23). Extraintestinal pathogenic Escherichia coli (ExPEC) is the causative agent of at least 80% of all uncomplicated UTIs. ExPEC strains that cause a UTI are called uropathogenic E. coli (UPEC). UPEC strains typically are members of phylogenetic group B2 or D and often exhibit specific O:K:H serotypes, as well as various combinations of virulence factors, including, among others, adhesins or fimbriae, siderophore systems, and toxins. The virulence-associated genes in UPEC are frequently clustered together in "pathogenicity islands" (PAIs) (25), and many UPEC isolates harbor more than one PAI. For instance, the prototypic UPEC clinical strain J96 (O4:K6) carries two PAIs, PAI I J96 and PAI II J96 (58). PAI I J96 is over 170 kb long and contains operons encoding alpha-hemolysin (hly) and Pap fimbriae (pap). PAI II J96 is 110 kb long and also contains an hly operon in addition to genes encoding Prs fimbriae (prs) and cytotoxic necrotizing factor type 1 (CNF1) (cnf 1 ) (6). Here, we hypothesized that the link between PAI II J96 and the urovirulence of E. coli strains may largely reflect the fact that these strains produce both alpha-hemolysin (referred to as hemolysin [Hly] here) and CNF1. ...

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A multinucleating Escherichia coli cytotoxin perturbs cell cycle in cultured epithelial cells

Cited by 15 publications

References 19 publications

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

Heterogeneous Family of Cyclomodulins: Smart Weapons That Allow Bacteria to Hijack the Eukaryotic Cell Cycle and Promote Infections

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 induces epithelial mesenchymal transition

Hemolysin of Uropathogenic Escherichia coli Evokes Extensive Shedding of the Uroepithelium and Hemorrhage in Bladder Tissue within the First 24 Hours after Intraurethral Inoculation of Mice

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