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

2019 ◽  
Vol 22 (2) ◽  
Author(s):  
Alessia Fabbri ◽  
Sara Travaglione ◽  
Francesca Rosadi ◽  
Giulia Ballan ◽  
Zaira Maroccia ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Cytotoxic Necrotizing Factor ◽  
Protein Toxin ◽  
Cytotoxic Necrotizing Factor 1

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 Cleavage of Escherichia coli Cytotoxic Necrotizing Factor 1 Is Required for Full Biologic Activity

2009 ◽  
Vol 77 (5) ◽  
pp. 1835-1841 ◽  
Author(s):  
Zeynep Knust ◽  
Britta Blumenthal ◽  
Klaus Aktories ◽  
Gudula Schmidt
Keyword(s):  
Escherichia Coli ◽  
Mammalian Cells ◽  
Catalytic Domain ◽  
Small Gtpases ◽  
Gtp Hydrolysis ◽  
Cytotoxic Necrotizing Factor ◽  
Endosomal Membrane ◽  
Protein Toxin ◽  
Late Endosomes ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Cytotoxic necrotizing factor 1 (CNF1) is a protein toxin produced by pathogenic Escherichia coli strains. CNF1 constitutively activates small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. The toxin is taken up into mammalian cells by receptor-mediated endocytosis and is delivered from late endosomes into the cytosol. Here, we show that an approximately 55-kDa fragment of CNF1, which contains the catalytic domain and an additional part of the toxin, is present in the cytosol. The processing of this fragment requires an acidic pH and insertion of the toxin into the endosomal membrane. We define the cleavage site region as the region located between amino acids 532 and 544 of CNF1. The data provide insight into the complex mechanism of uptake of bacterial toxins into mammalian cells.

Rho-activating Escherichia coli cytotoxic necrotizing factor 1: macropinocytosis of apoptotic bodies in human epithelial cells

2001 ◽  
Vol 291 (6-7) ◽  
pp. 551-554 ◽  
Author(s):  
Alessia Fabbri ◽  
Loredana Falzano ◽  
Sara Travaglione ◽  
Annarita Stringaro ◽  
Walter Malorni ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Apoptotic Bodies ◽  
Cytotoxic Necrotizing Factor ◽  
Human Epithelial Cells ◽  
Cytotoxic Necrotizing Factor 1

scholarly journals High Affinity Binding of Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) to Lu/BCAM Adhesion Glycoprotein

Toxins ◽  
2017 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Franziska Reppin ◽  
Sylvie Cochet ◽  
Wassim El Nemer ◽  
Günter Fritz ◽  
Gudula Schmidt
Keyword(s):  
Escherichia Coli ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
Cytotoxic Necrotizing Factor ◽  
High Affinity ◽  
Cytotoxic Necrotizing Factor 1

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 Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the Akt/IκB Kinase Pathway: Role of Nuclear Factor-κB and Bcl-2

2007 ◽  
Vol 18 (7) ◽  
pp. 2735-2744 ◽  
Author(s):  
Alessandro Giamboi Miraglia ◽  
Sara Travaglione ◽  
Stefania Meschini ◽  
Loredana Falzano ◽  
Paola Matarrese ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Nuclear Factor Κb ◽  
Ultraviolet B ◽  
Bacterial Toxin ◽  
Nuclear Factor ◽  
Mitochondrial Network ◽  
Cytotoxic Necrotizing Factor ◽  
Protein Toxin ◽  
Iκb Kinase ◽  
Cytotoxic Necrotizing Factor 1

Cytotoxic necrotizing factor 1 (CNF1) is a protein toxin produced by some pathogenic strains of Escherichia coli that specifically activates Rho, Rac, and Cdc42 GTPases. We previously reported that this toxin prevents the ultraviolet-B–induced apoptosis in epithelial cells, with a mechanism that remained to be defined. In this work, we show that the proteasomal degradation of the Rho GTPase is necessary to achieve cell death protection, because inhibition of Rho degradation abolishes the prosurvival activity of CNF1. We hypothesize that Rho inactivation allows the activity of Rac to become dominant. This in turn leads to stimulation of the phosphoinositide 3-kinase/Akt/IκB kinase/nuclear factor-κB prosurvival pathway and to a remarkable modification in the architecture of the mitochondrial network, mainly consisting in the appearance of elongated and interconnected mitochondria. Importantly, we found that Bcl-2 silencing reduces the ability of CNF1 to protect cells against apoptosis and that it also prevents the CNF1-induced mitochondrial changes. It is worth noting that the ability of a bacterial toxin to induce such a remodeling of the mitochondrial network is herein reported for the first time. The possible pathophysiological relevance of this finding is discussed.

scholarly journals Serogroups and virulence genes of Escherichia coli isolated from psittacine birds

2011 ◽  
Vol 31 (10) ◽  
pp. 916-921 ◽  
Author(s):  
Terezinha Knöbl ◽  
André B.S Saidenberg ◽  
Andrea M Moreno ◽  
Tânia A.T Gomes ◽  
Mônica A.M Vieira ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Virulence Genes ◽  
Serum Resistance ◽  
Temperature Sensitive ◽  
E Coli ◽  
Cytotoxic Necrotizing Factor ◽  
Heat Stable ◽  
Genes Encoding ◽  
Cytotoxic Necrotizing Factor 1

Escherichia coli isolates from 24 sick psittacine birds were serogrouped and investigated for the presence of genes encoding the following virulence factors: attaching and effacing (eae), enteropathogenic E. coli EAF plasmid (EAF), pili associated with pyelonephritis (pap), S fimbriae (sfa), afimbrial adhesin (afa), capsule K1 (neu), curli (crl, csgA), temperature-sensitive hemagglutinin (tsh), enteroaggregative heat-stable enterotoxin-1 (astA), heat-stable enterotoxin -1 heat labile (LT) and heat stable (STa and STb) enterotoxins, Shiga-like toxins (stx1 and stx2), cytotoxic necrotizing factor 1 (cnf1), haemolysin (hly), aerobactin production (iuc) and serum resistance (iss). The results showed that the isolates belonged to 12 serogroups: O7; O15; O21; O23; O54; O64; O76; O84; O88; O128; O152 and O166. The virulence genes found were: crl in all isolates, pap in 10 isolates, iss in seven isolates, csgA in five isolates, iuc and tsh in three isolates and eae in two isolates. The combination of virulence genes revealed 11 different genotypic patterns. All strains were negative for genes encoding for EAF, EAEC, K1, sfa, afa, hly, cnf, LT, STa, STb, stx1 and stx2. Our findings showed that some E. coli isolated from psittacine birds present the same virulence factors as avian pathogenic E. coli (APEC), uropathogenic E. coli (UPEC) and Enteropathogenic E. coli (EPEC) pathotypes.

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