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Antimicrobial Agents and Chemotherapy, September 2002, p. 2784-2790, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2784-2790.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The LisRK Signal Transduction System Determines the Sensitivity of Listeria monocytogenes to Nisin and Cephalosporins

Paul D. Cotter, Caitriona M. Guinane, and Colin Hill*

Department of Microbiology and National Food Biotechnology Centre, University College Cork, Cork, Ireland

Received 23 January 2002/ Returned for modification 29 March 2002/ Accepted 20 May 2002

The Listeria monocytogenes two-component signal transduction system, LisRK, initially identified in strain LO28, plays a significant role in the virulence potential of this important food-borne pathogen. Here, it is shown that, in addition to its major contribution in responding to ethanol, pH, and hydrogen peroxide stresses, LisRK is involved in the ability of the cell to tolerate important antimicrobials used in food and in medicine, e.g., the lantibiotic nisin and the cephalosporin family of antibiotics. A {Delta}lisK mutant (lacking the LisK histidine kinase sensor component) displays significantly enhanced resistance to the lantibiotic nisin, a greatly enhanced sensitivity to the cephalosporins, and a large reduction in the expression of three genes thought to encode a penicillin-binding protein, another histidine kinase (other than LisK), and a protein of unknown function. Confirmation of the role of LisRK was obtained when the response regulator, LisR, was overexpressed using both constitutive and inducible (nisin-controlled expression) systems. Under these conditions we observed a reversion of the {Delta}lisK mutant to wild-type growth kinetics in the presence of nisin. It was also found that overexpression of LisR complemented the reduced expression of two of the aforementioned genes. These results demonstrate the important role of LisRK in the response of L. monocytogenes to a number of antimicrobial agents.


* Corresponding author. Mailing address: Department of Microbiology, University College Cork, Cork, Ireland. Phone: 353-21-4902397. Fax: 353-21-4903101. E-mail: c.hill{at}ucc.ie.


Antimicrobial Agents and Chemotherapy, September 2002, p. 2784-2790, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2784-2790.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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