Previous Article | Next Article 
Infection and Immunity, April 2004, p. 2288-2302, Vol. 72, No. 4
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.4.2288-2302.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Identification of a Novel Citrobacter rodentium Type III Secreted Protein, EspI, and Roles of This and Other Secreted Proteins in Infection
Rosanna Mundy,1 Liljana Petrovska,1 Katherine Smollett,1 Nandi Simpson,1 Rebecca K. Wilson,1 Jun Yu,1 Xuanlin Tu,2 Ilan Rosenshine,2 Simon Clare,1 Gordon Dougan,1 and Gad Frankel1*
Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College, London SW7 2AZ, United Kingdom,1
Department of Molecular Genetics and Biotechnology, Faculty of Medicine, The Hebrew University, Jerusalem 91120 Israel2
Received 13 October 2003/
Returned for modification 29 December 2003/
Accepted 8 January 2004
Citrobacter rodentium is a member of a group of pathogens that colonize the lumen of the host gastrointestinal tract via attaching and effacing (A/E) lesion formation. C. rodentium, which causes transmissible colonic hyperplasia in mice, is used as an in vivo model system for the clinically significant A/E pathogens enterohemorrhagic and enteropathogenic Escherichia coli. These bacteria all contain a pathogenicity island called the locus of enterocyte effacement (LEE), which encodes a type III secretion system that is designed to deliver effector proteins into eukaryotic host cells. These effectors are involved in the subversion of host eukaryotic cell functions to the benefit of the bacterium. In this study we used mutant strains to determine the effects of the C. rodentium LEE-encoded effectors EspF, EspG, EspH, and Map on virulence in the mouse model. In addition, we identified a novel secreted protein, EspI encoded outside the LEE, whose secretion is also dependent on a functional type III secretion system. Mutant strains with each of the effectors investigated were found to be outcompeted by wild-type bacteria in mixed-infection experiments in vivo, although the effects of EspF and EspH were only subtle. In single-infection experiments, we found that EspF, EspG, and EspH are not required for efficient colonization of the mouse colon or for the production of hyperplasia. In contrast, strains producing EspI and Map had significant colonization defects and resulted in dramatically reduced levels of hyperplasia, and they exhibited very different growth dynamics in mice than the wild-type strain exhibited.
* Corresponding author. Mailing address: Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College, London SW7 2AZ, United Kingdom. Phone: 44 020 2594 5253. Fax: 44 020 5794 3069. E-mail:
g.frankel{at}imperial.ac.uk.
Editor: A. D. O'Brien
Infection and Immunity, April 2004, p. 2288-2302, Vol. 72, No. 4
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.4.2288-2302.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Arbeloa, A., Blanco, M., Moreira, F. C., Bulgin, R., Lopez, C., Dahbi, G., Blanco, J. E., Mora, A., Alonso, M. P., Mamani, R. C., Gomes, T. A. T., Blanco, J., Frankel, G.
(2009). Distribution of espM and espT among enteropathogenic and enterohaemorrhagic Escherichia coli. J Med Microbiol
58: 988-995
[Abstract]
[Full Text]
-
Hemrajani, C., Marches, O., Wiles, S., Girard, F., Dennis, A., Dziva, F., Best, A., Phillips, A. D., Berger, C. N., Mousnier, A., Crepin, V. F., Kruidenier, L., Woodward, M. J., Stevens, M. P., La Ragione, R. M., MacDonald, T. T., Frankel, G.
(2008). Role of NleH, a Type III Secreted Effector from Attaching and Effacing Pathogens, in Colonization of the Bovine, Ovine, and Murine Gut. Infect. Immun.
76: 4804-4813
[Abstract]
[Full Text]
-
Su, M. S.-W., Kao, H.-C., Lin, C.-N., Syu, W.-J.
(2008). Gene l0017 encodes a second chaperone for EspA of enterohaemorrhagic Escherichia coli O157 : H7. Microbiology
154: 1094-1103
[Abstract]
[Full Text]
-
Garcia-Angulo, V. A., Deng, W., Thomas, N. A., Finlay, B. B., Puente, J. L.
(2008). Regulation of Expression and Secretion of NleH, a New Non-Locus of Enterocyte Effacement-Encoded Effector in Citrobacter rodentium. J. Bacteriol.
190: 2388-2399
[Abstract]
[Full Text]
-
Coombes, B. K., Wickham, M. E., Mascarenhas, M., Gruenheid, S., Finlay, B. B., Karmali, M. A.
(2008). Molecular Analysis as an Aid To Assess the Public Health Risk of Non-O157 Shiga Toxin-Producing Escherichia coli Strains. Appl. Environ. Microbiol.
74: 2153-2160
[Abstract]
[Full Text]
-
Abe, H., Miyahara, A., Oshima, T., Tashiro, K., Ogura, Y., Kuhara, S., Ogasawara, N., Hayashi, T., Tobe, T.
(2008). Global Regulation by Horizontally Transferred Regulators Establishes the Pathogenicity of Escherichia coli. DNA Res
15: 25-38
[Abstract]
[Full Text]
-
Kendall, M. M., Rasko, D. A., Sperandio, V.
(2007). Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2, Autoinducer-3, and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli. Infect. Immun.
75: 4875-4884
[Abstract]
[Full Text]
-
Creuzburg, K., Schmidt, H.
(2007). Molecular Characterization and Distribution of Genes Encoding Members of the Type III Effector NleA Family among Pathogenic Escherichia coli Strains. J. Clin. Microbiol.
45: 2498-2507
[Abstract]
[Full Text]
-
Roe, A. J., Tysall, L., Dransfield, T., Wang, D., Fraser-Pitt, D., Mahajan, A., Constandinou, C., Inglis, N., Downing, A., Talbot, R., Smith, D. G. E., Gally, D. L.
(2007). Analysis of the expression, regulation and export of NleA-E in Escherichia coli O157 : H7. Microbiology
153: 1350-1360
[Abstract]
[Full Text]
-
Vidal, J. E., Navarro-Garcia, F.
(2006). Efficient Translocation of EspC into Epithelial Cells Depends on Enteropathogenic Escherichia coli and Host Cell Contact. Infect. Immun.
74: 2293-2303
[Abstract]
[Full Text]
-
Kelly, M., Hart, E., Mundy, R., Marches, O., Wiles, S., Badea, L., Luck, S., Tauschek, M., Frankel, G., Robins-Browne, R. M., Hartland, E. L.
(2006). Essential Role of the Type III Secretion System Effector NleB in Colonization of Mice by Citrobacter rodentium. Infect. Immun.
74: 2328-2337
[Abstract]
[Full Text]
-
Luo, W., Donnenberg, M. S.
(2006). Analysis of the Function of Enteropathogenic Escherichia coli EspB by Random Mutagenesis. Infect. Immun.
74: 810-820
[Abstract]
[Full Text]
-
Ogura, Y., Kurokawa, K., Ooka, T., Tashiro, K., Tobe, T., Ohnishi, M., Nakayama, K., Morimoto, T., Terajima, J., Watanabe, H., Kuhara, S., Hayashi, T.
(2006). Complexity of the Genomic Diversity in Enterohemorrhagic Escherichia coli O157 Revealed by the Combinational Use of the O157 Sakai OligoDNA Microarray and the Whole Genome PCR scanning. DNA Res
13: 3-14
[Abstract]
[Full Text]
-
Creuzburg, K., Recktenwald, J., Kuhle, V., Herold, S., Hensel, M., Schmidt, H.
(2005). The Shiga Toxin 1-Converting Bacteriophage BP-4795 Encodes an NleA-Like Type III Effector Protein. J. Bacteriol.
187: 8494-8498
[Abstract]
[Full Text]
-
Marches, O., Wiles, S., Dziva, F., La Ragione, R. M., Schuller, S., Best, A., Phillips, A. D., Hartland, E. L., Woodward, M. J., Stevens, M. P., Frankel, G.
(2005). Characterization of Two Non-Locus of Enterocyte Effacement-Encoded Type III-Translocated Effectors, NleC and NleD, in Attaching and Effacing Pathogens. Infect. Immun.
73: 8411-8417
[Abstract]
[Full Text]
-
Matsuzawa, T., Kuwae, A., Abe, A.
(2005). Enteropathogenic Escherichia coli Type III Effectors EspG and EspG2 Alter Epithelial Paracellular Permeability. Infect. Immun.
73: 6283-6289
[Abstract]
[Full Text]
-
Girard, F., Oswald, I. P., Taranu, I., Helie, P., Appleyard, G. D., Harel, J., Fairbrother, J. M.
(2005). Host Immune Status Influences the Development of Attaching and Effacing Lesions in Weaned Pigs. Infect. Immun.
73: 5514-5523
[Abstract]
[Full Text]
-
Naylor, S. W., Roe, A. J., Nart, P., Spears, K., Smith, David. G. E., Low, J. C., Gally, D. L.
(2005). Escherichia coli O157 : H7 forms attaching and effacing lesions at the terminal rectum of cattle and colonization requires the LEE4 operon. Microbiology
151: 2773-2781
[Abstract]
[Full Text]
-
Kanack, K. J., Crawford, J. A., Tatsuno, I., Karmali, M. A., Kaper, J. B.
(2005). SepZ/EspZ Is Secreted and Translocated into HeLa Cells by the Enteropathogenic Escherichia coli Type III Secretion System. Infect. Immun.
73: 4327-4337
[Abstract]
[Full Text]
-
Garmendia, J., Frankel, G., Crepin, V. F.
(2005). Enteropathogenic and Enterohemorrhagic Escherichia coli Infections: Translocation, Translocation, Translocation. Infect. Immun.
73: 2573-2585
[Full Text]
-
Crepin, V. F., Shaw, R., Abe, C. M., Knutton, S., Frankel, G.
(2005). Polarity of Enteropathogenic Escherichia coli EspA Filament Assembly and Protein Secretion. J. Bacteriol.
187: 2881-2889
[Abstract]
[Full Text]
-
Wei, O. L., Hilliard, A., Kalman, D., Sherman, M.
(2005). Mast Cells Limit Systemic Bacterial Dissemination but Not Colitis in Response to Citrobacter rodentium. Infect. Immun.
73: 1978-1985
[Abstract]
[Full Text]
-
Deng, W., Li, Y., Hardwidge, P. R., Frey, E. A., Pfuetzner, R. A., Lee, S., Gruenheid, S., Strynakda, N. C. J., Puente, J. L., Finlay, B. B.
(2005). Regulation of Type III Secretion Hierarchy of Translocators and Effectors in Attaching and Effacing Bacterial Pathogens. Infect. Immun.
73: 2135-2146
[Abstract]
[Full Text]
-
Ritchie, J. M., Waldor, M. K.
(2005). The Locus of Enterocyte Effacement-Encoded Effector Proteins All Promote Enterohemorrhagic Escherichia coli Pathogenicity in Infant Rabbits. Infect. Immun.
73: 1466-1474
[Abstract]
[Full Text]
-
Dahan, S., Wiles, S., La Ragione, R. M., Best, A., Woodward, M. J., Stevens, M. P., Shaw, R. K., Chong, Y., Knutton, S., Phillips, A., Frankel, G.
(2005). EspJ Is a Prophage-Carried Type III Effector Protein of Attaching and Effacing Pathogens That Modulates Infection Dynamics. Infect. Immun.
73: 679-686
[Abstract]
[Full Text]
-
Nagai, T., Abe, A., Sasakawa, C.
(2005). Targeting of Enteropathogenic Escherichia coli EspF to Host Mitochondria Is Essential for Bacterial Pathogenesis: CRITICAL ROLE OF THE 16TH LEUCINE RESIDUE IN EspF. J. Biol. Chem.
280: 2998-3011
[Abstract]
[Full Text]
-
Henderson, I. R., Navarro-Garcia, F., Desvaux, M., Fernandez, R. C., Ala'Aldeen, D.
(2004). Type V Protein Secretion Pathway: the Autotransporter Story. Microbiol. Mol. Biol. Rev.
68: 692-744
[Abstract]
[Full Text]
-
Dziva, F., van Diemen, P. M., Stevens, M. P., Smith, A. J., Wallis, T. S.
(2004). Identification of Escherichia coli O157 : H7 genes influencing colonization of the bovine gastrointestinal tract using signature-tagged mutagenesis. Microbiology
150: 3631-3645
[Abstract]
[Full Text]
-
Mundy, R., Jenkins, C., Yu, J., Smith, H., Frankel, G.
(2004). Distribution of espI among clinical enterohaemorrhagic and enteropathogenic Escherichia coli isolates. J Med Microbiol
53: 1145-1149
[Abstract]
[Full Text]
-
Dahan, S., Knutton, S., Shaw, R. K., Crepin, V. F., Dougan, G., Frankel, G.
(2004). Transcriptome of Enterohemorrhagic Escherichia coli O157 Adhering to Eukaryotic Plasma Membranes. Infect. Immun.
72: 5452-5459
[Abstract]
[Full Text]
-
Charpentier, X., Oswald, E.
(2004). Identification of the Secretion and Translocation Domain of the Enteropathogenic and Enterohemorrhagic Escherichia coli Effector Cif, Using TEM-1 {beta}-Lactamase as a New Fluorescence-Based Reporter. J. Bacteriol.
186: 5486-5495
[Abstract]
[Full Text]