This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gauthier, A.
Right arrow Articles by Finlay, B. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gauthier, A.
Right arrow Articles by Finlay, B. B.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2005, p. 4101-4109, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4101-4109.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Transcriptional Inhibitor of Virulence Factors in Enteropathogenic Escherichia coli

Annick Gauthier ,1,{dagger},{ddagger} Marilyn L. Robertson,1,{dagger} Michael Lowden,1 J. Antonio Ibarra,2 José Luis Puente,2 and B. Brett Finlay1*

Michael Smith Laboratories and Departments of Biochemistry and Microbiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada,1 Departamento de Biología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico2

Received 24 January 2005/ Returned for modification 29 April 2005/ Accepted 18 July 2005

The type III secretion system (TTSS) is a key virulence mechanism of many important gram-negative bacterial pathogens. The TTSS is conserved among different bacterial pathogens, and mutations and deletions to the system significantly decrease virulence, making the TTSS an important potential therapeutic target. We have developed a high-throughput assay to search for inhibitors of the TTSS. We screened a commercial library of 20,000 small molecules for their ability to inhibit type III secretion by enteropathogenic Escherichia coli (EPEC). After discarding compounds that had no effect on secretion, inhibited bacterial growth, and/or caused degradation of EPEC-secreted proteins, the search was focused on a class of compounds that, while not direct inhibitors of type III secretion, inhibit expression of TTSS-related genes and other genes involved in virulence. This class of compounds does not affect bacterial viability or motility, indicating that it is not significantly affecting the expression of essential genes and is specific to virulence-associated genes. Transcriptional fusion assays confirmed that virulence-associated promoters were more sensitive to inhibition by this class of compounds. Overall, we have identified a class of compounds that can be used as a tool to probe the mechanism(s) that regulates virulence gene expression in EPEC.

* Corresponding author. Mailing address: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Phone: 604 822 2210. Fax: 604 822 9830. E-mail: bfinlay{at}interchange.ubc.ca.

{dagger} A.G. and M.L.R. contributed equally to this work.

{ddagger} Present address: Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, NY 10021.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4101-4109, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4101-4109.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tree, J. J., Wang, D., McInally, C., Mahajan, A., Layton, A., Houghton, I., Elofsson, M., Stevens, M. P., Gally, D. L., Roe, A. J. (2009). Characterization of the Effects of Salicylidene Acylhydrazide Compounds on Type III Secretion in Escherichia coli O157:H7. Infect. Immun. 77: 4209-4220 [Abstract] [Full Text]  
  • Puiac, S., Negrea, A., Richter-Dahlfors, A., Plant, L., Rhen, M. (2009). Omeprazole Antagonizes Virulence and Inflammation in Salmonella enterica-Infected RAW264.7 Cells. Antimicrob. Agents Chemother. 53: 2402-2409 [Abstract] [Full Text]  
  • Pan, N. J., Brady, M. J., Leong, J. M., Goguen, J. D. (2009). Targeting Type III Secretion in Yersinia pestis. Antimicrob. Agents Chemother. 53: 385-392 [Abstract] [Full Text]  
  • Veenendaal, A. K. J., Sundin, C., Blocker, A. J. (2009). Small-Molecule Type III Secretion System Inhibitors Block Assembly of the Shigella Type III Secreton. J. Bacteriol. 191: 563-570 [Abstract] [Full Text]  
  • Coburn, B., Sekirov, I., Finlay, B. B. (2007). Type III Secretion Systems and Disease. Clin. Microbiol. Rev. 20: 535-549 [Abstract] [Full Text]  
  • Mellies, J. L., Barron, A. M. S., Carmona, A. M. (2007). Enteropathogenic and Enterohemorrhagic Escherichia coli Virulence Gene Regulation. Infect. Immun. 75: 4199-4210 [Full Text]  
  • Negrea, A., Bjur, E., Ygberg, S. E., Elofsson, M., Wolf-Watz, H., Rhen, M. (2007). Salicylidene Acylhydrazides That Affect Type III Protein Secretion in Salmonella enterica Serovar Typhimurium. Antimicrob. Agents Chemother. 51: 2867-2876 [Abstract] [Full Text]  
  • Hudson, D. L., Layton, A. N., Field, T. R., Bowen, A. J., Wolf-Watz, H., Elofsson, M., Stevens, M. P., Galyov, E. E. (2007). Inhibition of Type III Secretion in Salmonella enterica Serovar Typhimurium by Small-Molecule Inhibitors. Antimicrob. Agents Chemother. 51: 2631-2635 [Abstract] [Full Text]  
  • Pinkner, J. S., Remaut, H., Buelens, F., Miller, E., Aberg, V., Pemberton, N., Hedenstrom, M., Larsson, A., Seed, P., Waksman, G., Hultgren, S. J., Almqvist, F. (2006). Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc. Natl. Acad. Sci. USA 103: 17897-17902 [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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»