scholarly journals Effects of the Escherichia coli Bacterial Toxin Cytotoxic Necrotizing Factor 1 on Different Human and Animal Cells: A Systematic Review

2021 ◽  
Vol 22 (22) ◽  
pp. 12610
Author(s):  
Francesca Carlini ◽  
Zaira Maroccia ◽  
Carla Fiorentini ◽  
Sara Travaglione ◽  
Alessia Fabbri
Keyword(s):  
Escherichia Coli ◽  
Rho Gtpases ◽  
Cultured Cells ◽  
Bacterial Toxin ◽  
Animal Cells ◽  
Eligibility Criteria ◽  
Cytotoxic Necrotizing Factor ◽  
Small Proteins ◽  
Cytotoxic Necrotizing Factor 1

Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic Escherichia coli extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.

scholarly journals Escherichia coli Cytotoxic Necrotizing Factor 1 Blocks Cell Cycle G2/M Transition in Uroepithelial Cells

2006 ◽  
Vol 74 (7) ◽  
pp. 3765-3772 ◽  
Author(s):  
Loredana Falzano ◽  
Perla Filippini ◽  
Sara Travaglione ◽  
Alessandro Giamboi Miraglia ◽  
Alessia Fabbri ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Rho Gtpases ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Eukaryotic Cell ◽  
Cytotoxic Necrotizing Factor ◽  
Cytoskeleton Organization ◽  
Protein Toxin ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Evidence is accumulating that a growing number of bacterial toxins act by modulating the eukaryotic cell cycle machinery. In this context, we provide evidence that a protein toxin named cytotoxic necrotizing factor 1 (CNF1) from uropathogenic Escherichia coli is able to block cell cycle G2/M transition in the uroepithelial cell line T24. CNF1 permanently activates the small GTP-binding proteins of the Rho family that, beside controlling the actin cytoskeleton organization, also play a pivotal role in a large number of other cellular processes, including cell cycle regulation. The results reported here show that CNF1 is able to induce the accumulation of cells in the G2/M phase by sequestering cyclin B1 in the cytoplasm and down-regulating its expression. The possible role played by the Rho GTPases in the toxin-induced cell cycle deregulation has been investigated and discussed. The activity of CNF1 on cell cycle progression can offer a novel view of E. coli pathogenicity.

scholarly journals Effect of Escherichia coli Cytotoxic Necrotizing Factor 1 on Repair of Human Bladder Cell Monolayers In Vitro

1999 ◽  
Vol 67 (7) ◽  
pp. 3657-3661 ◽  
Author(s):  
Michael D. Island ◽  
Xaioling Cui ◽  
John W. Warren
Keyword(s):  
Escherichia Coli ◽  
Bladder Epithelium ◽  
Cell Monolayers ◽  
E Coli ◽  
Cytotoxic Necrotizing Factor ◽  
Bladder Cell ◽  
Bladder Cells ◽  
Vitro Model ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT We hypothesized that Escherichia coli cytotoxic necrotizing factor 1 (CNF1) might impair migration or proliferation of bladder cells and could potentially interfere with repair of the bladder epithelium. Using experimentally wounded human T24 bladder epithelial cell monolayers as an in vitro model, we found that both the number of T24 cells and the maximum distance they migrated into wounded regions was significantly decreased by bacterial extracts containingE. coli CNF1.

scholarly journals Cytotoxicity of Hemolytic, Cytotoxic Necrotizing Factor 1-Positive and -Negative Escherichia coli to Human T24 Bladder Cells

1998 ◽  
Vol 66 (7) ◽  
pp. 3384-3389 ◽  
Author(s):  
Michael D. Island ◽  
Xiaoling Cui ◽  
Betsy Foxman ◽  
Carl F. Marrs ◽  
Walter E. Stamm ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Types ◽  
Blue Staining ◽  
Detectable Effect ◽  
E Coli ◽  
Cytotoxic Necrotizing Factor ◽  
Bladder Cell ◽  
Bladder Cells ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Approximately one-half of Escherichia coli isolates from patients with cystitis or pyelonephritis produce the pore-forming cytotoxin hemolysin, a molecule with the capacity to lyse erythrocytes and a range of nucleated cell types. A second toxin, cytotoxic necrotizing factor 1 (CNF1), is found in approximately 70% of hemolytic, but rarely in nonhemolytic, isolates. To evaluate the potential interplay of these two toxins, we used epidemiological and molecular biologic techniques to compare the cytotoxicity of hemolytic, CNF1+, and CNF1− cystitis strains toward human T24 bladder epithelial cells in vitro. A total of 29 isolates from two collections of cystitis-associated E. coli were evaluated by using methylene blue staining of bladder monolayers at 1-h intervals after inoculation with each strain. Most (20 of 29) isolates damaged or destroyed the T24 monolayer (less than 50% remaining) within 4 h after inoculation. As a group, CNF1+ isolates from one collection (11 strains) were less cytotoxic at 4 h than the CNF1− strains in that collection (P = 0.009), but this pattern was not observed among isolates from the second collection (18 strains). To directly evaluate the role of CNF1 in cytotoxicity of hemolytic E. coli without the variables present in multiple clinical isolates, we constructed mutants defective in production of CNF1. Compared to the CNF1+ parental isolates, no change in cytotoxicity was detected in thesecnf1 mutants. Our results indicate that CNF1 does not have a detectable effect on the ability of hemolytic E. coli to damage human bladder cell monolayers in vitro.

scholarly journals Deamidation of Cdc42 and Rac by Escherichia coliCytotoxic Necrotizing Factor 1: Activation of c-Jun N-Terminal Kinase in HeLa Cells

1999 ◽  
Vol 67 (2) ◽  
pp. 496-503 ◽  
Author(s):  
M. Lerm ◽  
J. Selzer ◽  
A. Hoffmeyer ◽  
U. R. Rapp ◽  
K. Aktories ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Mass ◽  
Hela Cells ◽  
Fold Increase ◽  
Gtpase Activating Protein ◽  
Intact Cells ◽  
Tryptic Peptides ◽  
Cytotoxic Necrotizing Factor ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Recently, Escherichia coli cytotoxic necrotizing factor 1 (CNF1) was shown to activate the low-molecular-mass GTPase RhoA by deamidation of Gln63, thereby inhibiting intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities (G. Schmidt, P. Sehr, M. Wilm, J. Selzer, M. Mann, and K. Aktories, Nature 387:725–729, 1997; G. Flatau, E. Lemichez, M. Gauthier, P. Chardin, S. Paris, C. Fiorentini, and P. Boquet, Nature 387:729–733, 1997). Here we report that in addition to RhoA, Cdc42 and Rac also are targets for CNF1 in vitro and in intact cells. Treatment of HeLa cells with CNF1 induced a transient formation of microspikes and formation of membrane ruffles. CNF1 caused a transient 10- to 50-fold increase in the activity of the c-Jun N-terminal kinase. Tryptic peptides of Cdc42 obtained from CNF1-treated cells by immunoprecipitation exhibited an increase in mass of 1 Da compared to control peptides, indicating the deamidation of glutamine 61 by the toxin. The same increase in mass was observed with the respective peptides obtained from CNF1-modified recombinant Cdc42 and Rac1. Modification of recombinant Cdc42 and Rac1 by CNF1 inhibited intrinsic and GAP-stimulated GTPase activities and retarded binding of 2′(3′)- O-(N -methylanthraniloyl)GDP. The data suggest that recombinant as well as cellular Cdc42 and Rac are substrates for CNF1.

scholarly journals Quinolones Induce Partial or Total Loss of Pathogenicity Islands in Uropathogenic Escherichia coli by SOS-Dependent or -Independent Pathways, Respectively

2006 ◽  
Vol 50 (2) ◽  
pp. 649-653 ◽  
Author(s):  
S. M. Soto ◽  
M. T. Jimenez de Anta ◽  
J. Vila
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Reca Protein ◽  
Total Loss ◽  
Pathogenicity Islands ◽  
E Coli ◽  
Cytotoxic Necrotizing Factor ◽  
Tract Infections ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Escherichia coli is the most common microorganism causing urinary tract infections. Quinolone-resistant E. coli strains have fewer virulence factors than quinolone-susceptible strains. Several urovirulence genes are located in pathogenicity islands (PAIs). We investigated the capacity of quinolones to induce loss of virulence factors such as hemolysin, cytotoxic necrotizing factor 1, P fimbriae, and autotransporter Sat included in PAIs in three uropathogenic E. coli strains. In a multistep selection, all strains lost hemolytic capacity at between 1 and 4 passages when they were incubated with subinhibitory concentrations of ciprofloxacin, showing a partial or total loss of the PAI containing the hly (hemolysin) and cnf-1 (cytotoxic necrotizing factor 1) genes. RecA− mutants were obtained from the two E. coli strains with partial or total loss of the PAI. The inactivation of the RecA protein affected only the partial loss of the PAI induced by quinolones. No spontaneous loss of PAIs was observed on incubation in the absence of quinolones in either the wild-type or mutant E. coli strains. Quinolones induce partial or total loss of PAIs in vitro in uropathogenic E. coli by SOS-dependent or -independent pathways, respectively.

scholarly journals Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder

2012 ◽  
Vol 81 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Tamako A. Garcia ◽  
Christy L. Ventura ◽  
Mark A. Smith ◽  
D. Scott Merrell ◽  
Alison D. O'Brien
Keyword(s):  
Escherichia Coli ◽  
Innate Immunity ◽  
Rho Gtpases ◽  
Negative Impact ◽  
Proinflammatory Response ◽  
Bladder Tissue ◽  
Content Type ◽  
Cytotoxic Necrotizing Factor ◽  
Expression Of Genes ◽  
Cytotoxic Necrotizing Factor 1

Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (HlyA1) are toxins produced by uropathogenicEscherichia coli(UPEC). We previously showed that these toxins contribute to the inflammation and tissue damage seen in a mouse model of ascending urinary tract infection. CNF1 constitutively activates small Rho GTPases by deamidation of a conserved glutamine residue, and HlyA1 forms pores in eukaryotic cell membranes. In this study, we used cDNA microarrays of bladder tissue isolated from mice infected intraurethrally with wild-type CP9, CP9cnf1, or CP9ΔhlyAto further evaluate the role that each toxin plays in the host response to UPEC. Regardless of the strain used, we found that UPEC itself elicited a significant change in host gene expression 24 h after inoculation. The largest numbers of upregulated genes were in the cytokine and chemokine signaling and Toll-like receptor signaling pathways. CNF1 exerted a strong positive influence on expression of genes involved in innate immunity and signal transduction and a negative impact on metabolism- and transport-associated genes. HlyA1 evoked an increase in expression of genes that encode innate immunity factors and a decrease in expression of genes involved in cytoskeletal and metabolic processes. Multiplex cytokine and myeloperoxidase assays corroborated our finding that a strong proinflammatory response was elicited by all strains tested. Bladders challenged intraurethrally with purified CNF1 displayed pathology similar to but significantly less intense than the pathology that we observed in CP9-challenged mice. Our data demonstrate substantial roles for CNF1 and HlyA1 in initiation of a strong proinflammatory response to UPEC in the bladder.

scholarly journals Characterization of cytotoxic necrotizing factor 1-producing Escherichia coli strains from faeces of healthy macaques

2009 ◽  
Vol 58 (10) ◽  
pp. 1354-1358 ◽  
Author(s):  
Heather R. Martin ◽  
Nancy S. Taylor ◽  
Ellen M. Buckley ◽  
Robert P. Marini ◽  
Mary M. Patterson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cytopathic Effect ◽  
Repetitive Element ◽  
E Coli ◽  
Cytotoxic Necrotizing Factor ◽  
Clinically Normal ◽  
Cytotoxic Necrotizing Factor 1 ◽  
Element Sequence

Twenty-five (27 %) of 92 clinically normal macaques were found to have β-haemolytic Escherichia coli isolated from their faeces. Five of six isolates chosen for further characterization had multiple antibiotic resistance and were PCR-positive for cytotoxic necrotizing factor 1 (cnf1) with a demonstrated cytopathic effect in vitro. By repetitive element sequence-based PCR genotyping, genetic similarity was established for selected isolates. We believe this to be the first report of E. coli strains producing CNF1 in non-human primates.

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