HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 10, 8761-8768, March 5, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/10/8761    most recent M312080200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perron, K. Articles by Köhler, T. Search for Related Content PubMed PubMed Citation Articles by Perron, K. Articles by Köhler, T. Social Bookmarking                      What's this?

CzcR-CzcS, a Two-component System Involved in Heavy Metal and Carbapenem Resistance in Pseudomonas aeruginosa^*

Karl Perron, Olivier Caille, Claude Rossier, Christian van Delden, Jean-Luc Dumas, and Thilo Köhler¶

From the Laboratory of Bacteriology and Microbial Ecology, Department of Botany and Plant Biology Sciences III and the Department of Genetics and Microbiology, Centre Médical Universitaire, University of Geneva, CH-1211 Geneva 4, Switzerland

Pseudomonas aeruginosa is an environmental bacterium involved in mineralization of organic matter. It is also an opportunistic pathogen able to cause serious infections in immunocompromised hosts. As such, it is exposed to xenobiotics including solvents, heavy metals, and antimicrobials. We studied the response of P. aeruginosa upon exposure to heavy metals or antibiotics to investigate whether common regulatory mechanisms govern resistance to both types of compounds. We showed that sublethal zinc concentrations induced resistance to zinc, cadmium, and cobalt, while lethal zinc concentrations selected mutants constitutively resistant to these heavy metals. Both zinc-induced and stable zinc-resistant strains were also resistant to the carbapenem antibiotic imipenem. On the other hand, only 20% of clones selected on imipenem were also resistant to zinc. Heavy metal resistance in the mutants could be correlated by quantitative real time PCR with increased expression of the heavy metal efflux pump CzcCBA and its cognate two-component regulator genes czcR-czcS. Western blot analysis revealed reduced expression of the basic amino acid and carbapenem-specific OprD porin in all imipenem-resistant mutants. Sequencing of the czcR-czcS DNA region in eight independent zinc- and imipenem-resistant mutants revealed the presence of the same V194L mutation in the CzcS sensor protein. Overexpression in a susceptible wild type strain of the mutated CzsS protein, but not of the wild type form, resulted in decreased oprD and increased czcC expression. We further show that zinc is released from latex urinary catheters into urine in amounts sufficient to induce carbapenem resistance in P. aeruginosa, possibly compromising treatment of urinary tract infections by this class of antibiotics.

Received for publication, November 4, 2003 , and in revised form, December 12, 2003.

^* This work was supported by Swiss National Science Foundation Grants Nos. 4049.063239/2 (to T. K.) and 3231-51940 and 3200-067262 (to C. v. D.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel.: 41-22-379-56-55; Fax: 41-22-379-57-02; E-mail: Thilo.Kohler{at}medecine.unige.ch.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Leedjarv, A. Ivask, and M. Virta Interplay of Different Transporters in the Mediation of Divalent Heavy Metal Resistance in Pseudomonas putida KT2440 J. Bacteriol., April 15, 2008; 190(8): 2680 - 2689. [Abstract] [Full Text] [PDF]

				M. A. Oberhardt, J. Puchalka, K. E. Fryer, V. A. P. Martins dos Santos, and J. A. Papin Genome-Scale Metabolic Network Analysis of the Opportunistic Pathogen Pseudomonas aeruginosa PAO1 J. Bacteriol., April 15, 2008; 190(8): 2790 - 2803. [Abstract] [Full Text] [PDF]

				O. Caille, C. Rossier, and K. Perron A Copper-Activated Two-Component System Interacts with Zinc and Imipenem Resistance in Pseudomonas aeruginosa J. Bacteriol., July 1, 2007; 189(13): 4561 - 4568. [Abstract] [Full Text] [PDF]

				H. Wu, F. Mao, V. Olman, and Y. Xu Hierarchical classification of functionally equivalent genes in prokaryotes Nucleic Acids Res., April 1, 2007; 35(7): 2125 - 2140. [Abstract] [Full Text] [PDF]

				S. Ballesta, M. C. Conejo, I. Garcia, J. M. Rodriguez-Martinez, C. Velasco, and A. Pascual Survival and resistance to imipenem of Pseudomonas aeruginosa on latex gloves J. Antimicrob. Chemother., May 1, 2006; 57(5): 1010 - 1012. [Full Text] [PDF]

				J. L. Ramos, M. Martinez-Bueno, A. J. Molina-Henares, W. Teran, K. Watanabe, X. Zhang, M. T. Gallegos, R. Brennan, and R. Tobes The TetR Family of Transcriptional Repressors Microbiol. Mol. Biol. Rev., June 1, 2005; 69(2): 326 - 356. [Abstract] [Full Text] [PDF]

				T. R. Walsh, M. A. Toleman, L. Poirel, and P. Nordmann Metallo-{beta}-Lactamases: the Quiet before the Storm? Clin. Microbiol. Rev., April 1, 2005; 18(2): 306 - 325. [Abstract] [Full Text] [PDF]