Transcriptional Inhibitor of Virulence Factors in EnteropathogenicEscherichia coli

Antimicrobial Agents and Chemotherapy - Tập 49 Số 10 - Trang 4101-4109 - 2005
Annick Gauthier1, Marilyn L. Robertson1, Michael J. Lowden1, J. Antonio Ibarra2, José L. Puente2, B. Brett Finlay1
1Michael Smith Laboratories and Departments of Biochemistry and Microbiology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
2Departamento de Biología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico

Tóm tắt

ABSTRACT

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 enteropathogenicEscherichia 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.

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Tài liệu tham khảo

10.1046/j.1365-2958.2001.02209.x

10.1128/CMR.16.3.365-378.2003

Creasey, E. A., R. M. Delahay, S. Daniell, and G. Frankel. 2003. Yeast two-hybrid system survey of interactions between LEE-encoded proteins of enteropathogenic E. coli. Microbiology148:2093-2106.

10.1073/pnas.98.4.1883

10.1046/j.1365-2958.1998.00798.x

10.1128/IAI.73.4.2135-2146.2005

10.1073/pnas.0400326101

10.1128/iai.58.6.1565-1571.1990

10.1128/IAI.68.11.6115-6126.2000

10.1046/j.1365-2958.1998.00783.x

10.1046/j.1365-2958.1999.01655.x

Gauthier, A., and B. B. Finlay. 2002. The hunt for type III secretion system inhibitors as potential antimicrobials. ASM News68:383-387.

10.1128/IAI.71.6.3310-3319.2003

10.1128/IAI.71.1.384-392.2003

10.1128/IAI.69.3.1231-1243.2001

10.1128/MMBR.62.2.379-433.1998

Kauppi, A. M., R. Nordfelth, U. Hägglund, H. Wolf-Watz, and M. Elofsson. 2003. Salicylanilides are potent inhibitors of type III secretion in Yersinia. Adv. Exp. Med. Biol.529:97-100.

10.1016/S1074-5521(03)00046-2

10.1111/j.1432-1033.1974.tb03677.x

10.1128/iai.65.7.2606-2612.1997

10.1016/S0092-8674(00)80437-7

10.1073/pnas.92.17.7991

10.1128/iai.57.4.1290-1298.1989

10.1073/pnas.85.18.6632

10.1021/ol0268337

10.1046/j.1365-2958.1999.01460.x

10.1073/pnas.92.5.1664

10.1046/j.1365-2958.1997.2311591.x

10.1046/j.1365-2958.1999.01473.x

10.1128/IAI.69.1.315-324.2001

10.1128/iai.41.3.1340-1351.1983

10.1517/14728222.5.3.327

10.1128/CMR.11.1.142

10.1111/j.1365-2958.2004.04333.x

Preston, G. M., N. Bertrand, and P. B. Rainey. 2001. Type III secretion in plant growth-promoting Pseudomonas fluorescens SBW25. Mol. Microbiol.41:999-1014.

10.1111/j.1365-2958.1996.tb02491.x

10.1128/JB.183.9.2823-2833.2001

10.1128/IAI.69.6.3523-3535.2001

10.1128/jb.178.22.6546-6554.1996

10.1016/S0890-8508(02)00108-1

10.1016/S0955-0674(00)00111-3

10.1046/j.1365-2958.1996.531415.x

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Antimicrobial Agents and Chemotherapy

Tập 49 Số 10

4101-4109

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