Abstract
Certain pathogenicEscherichia coli strains elaborate a toxin, the cytotoxic necrotizing factor type 1 (CNF1). CNF1 covalently and specifically modifies the p21 Rho GTP-binding protein in mammalian cells by deamidation of the p21 Rho glutamine 63. CNF1 modification of Rho leads to permanent activation of the GTP-binding protein by blocking intrinsic and RhoGAP GTPase activities. Rho activation by CNF1 induces reorganization of the actin cytoskeleton into large stress fibers and the multiplication of focal contact points. Deamidation is a new catalytic activity described for an intracellularly acting toxin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Allured V.S., Collier R.J., Carroll S.F., Mckay D.B.: Structure of exotoxin A ofPseudomonas aeruginosa at 3.0 Å resolution.Proc. Nat. Acad. Sci. USA 83, 1320–1324 (1986).
Blanco J., Blanco M., Alonso M.P., Blanco J.E., Gonzales E.A., Garabal J.I.: Characteristics of haemolyticEscherichia coli with particular reference to production of cytotoxic necrotizing factor type 1.Res. Microbiol. 143, 869–878 (1992).
Blum G., Falbo V., Caprioli A., Hacker J.: Gene clusters encoding the cytotoxic necrotizing factort type 1 Prs fimbriae and a hemolysin from the pathogenicity island II of the uropathogenicEscherichia coli strain J96.FEMS Microbiol. Lett. 126, 189–196 (1995).
Caprioli A., Falbo V., Roda L.G., Ruggeri F.M., Zona C.: Partial purification and characterization of anEscherichia coli toxic factor that induces morphological cell alterations.Infect. Immun. 39, 1300–1306 (1983).
Cornelis G., Wolf-Watz H.: TheYersinia Yop virulon: a bacterial system for subverting eucaryotic cells.Mol. Microbiol. 23, 861–867 (1997).
Donelli G., Fiorentini C.L., Falzano L., Pouchelet M., Oswald E., Boquet P.: Effects induced by the cytotoxic necrotizing factor 1 (CNF1) from pathogenicE. coli on cultured epithelial cells.Zbl. Bakteriol. Suppl. 24, 60–71 (1994).
Falbo V., Pace T., Picci L., Pizzi E., Caprioli A.: Isolation and nucleotide sequence of the gene encoding cytotoxic necrotizing factor type 1.Infect. Immun. 61, 4909–4914 (1993).
Falzano L., Fiorentini C., Donelli G., Michel E., Kocks C., Cossart P., Cabanie L., Oswald E., Boquet P.: Induction of phagocytic behaviour in human epithelial cells byEscherichia coli cytotoxic necrotizing factor type 1.Mol. Microbiol. 9, 1247–1254 (1993).
Fiorentini C., Arancia G., Caprioli A., Falbo V., Ruggeri F.M., Donelli G. Cytoskeletal changes induced in Hep-2 cells by the cytotoxic necrotizing factor ofEscherichia coli.Toxicon 26, 1047–1056 (1988).
Fiorentini C., Donelli G., Matarrese P., Fabbri A., Paradisi S., Boquet P.:Escherichia coli cytotoxic necrotizing factor 1: evidence for induction of actin assembly by constitutive activation of the p21 Rho GTPase.Infect. Immun. 63, 3936–3944 (1995).
Fiorentini C., Giry M., Donelli G., Falzano L., Aullo P., Boquet P.:E. coli cytotoxic necrotizing factor 1 increases actin assemblyvia the p21 Rho GTPase.Zbl. Bakteriol. Suppl. 24, 404–405 (1994).
Flatau G., Lemichez E., Gauthier M., Chardin P., Paris S., Fiorentini C., Boquet P.: Toxin-induced activation of the G-protein Rho by deamidation of glutamine.Nature 387, 729–733 (1997).
Lemichez E., Flatau G., Bruzzone M., Boquet P., Gauthier M.: Molecular localization of theEscherichia coli cytotoxic necrotizing factor CNF1 cell-binding and catalytic domains.Mol. Microbiol. 24, 1061–1070 (1997).
Michel E., Reich K.A., Favier R., Berche P., Cossart P.: Attenuated mutants of the intracellular bacteriumListeria monocytogenes obtained by single amino acids substitutions in listeriolysin O..Mol. Microbiol. 4, 2167–2178 (1990).
Nobes C.D., Hall A.: Rho, Rac and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia and filopodia.Cell 81, 1–20 (1995).
Oswald E., Sugai M., Labigne A., Wu H.C., Fiorentini C., Boquet P., O'Brien A.: Cytotoxic necrotizing factor type 2 produced by virulentEscherichia coli modifies the small GTP-binding protein Rho involved in assembly of actin stress fibers.Proc. Nat. Acad. Sci. USA 91, 3814–3818 (1994).
Ridley A.J., Hall A.: The small GTP-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.Cell 70, 389–399 (1992).
Ridley A.J., Paterson H.F., Johnston C.L., Diekmann D., Hall A.: The small GTP-binding protein Rac regulates growth factor-induced membrane ruffling.Cell 70, 1942–1952 (1995).
Rittinger K., Walker P.A., Eccleston J.F., Smerdon S.J., Gamblin S.J.: Structure at 1.65 Å of RhoA and its GTPase-activating protein in complex with a transition state analog.Nature 389, 758–762 (1997).
de Rycke J., Guillot J.F., Boivin R.: Cytotoxins in non-enterotoxigenic strains ofEscherichia coli isolated from faeces of diarrheic calves.Vet. Microbiol. 15, 137–157 (1987).
de Rycke J., Gonzalez E.A., Blanco J., Oswald E., Blanco M., Boivin R.: Evidence for two types of cytotoxic necrotizing factor in human and animal clinical isolates.J. Clin. Microbiol. 28, 694–699 (1990).
Schmidt G., Sehr P., Wilm M., Selzer J., Mann M., Aktories A.: Gln 63 of Rho is deamidated byEscherichia coli cytotoxic necrotizing factor 1.Nature 387, 725–728 (1997).
Swenson D.L., Bukanov N.O., Berg D.E., Welch R.A.: Two pathogenicity islands in uropathogenicEscherichia coli J96: cosmid cloning and sample sequencing.Infect. Immun. 64, 3736–3743 (1996).
Tapon N., Hall A.: Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton.Curr. Opin. Cell Biol. 9, 86–92 (1997).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Boquet, P. Cytotoxic necrotizing factor 1 fromEscherichia coli: a toxin with a new intracellular activity for eukaryotic cells. Folia Microbiol 43, 285–289 (1998). https://doi.org/10.1007/BF02818614
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02818614