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Antimicrobial Agents and Chemotherapy, February 2008, p. 505-512, Vol. 52, No. 2
0066-4804/08/$08.00+0     doi:10.1128/AAC.00504-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Role of a Sodium-Dependent Symporter Homologue in the Thermosensitivity of β-Lactam Antibiotic Resistance and Cell Wall Composition in Staphylococcus aureus{triangledown}

Krzysztof Sieradzki, Marilyn Chung, and Alexander Tomasz*

The Rockefeller University, 1230 York Avenue, New York, New York 10021

Received 13 April 2007/ Returned for modification 2 July 2007/ Accepted 15 November 2007

Expression of high-level β-lactam resistance is known to be thermosensitive in many methicillin-resistant Staphylococcus aureus (MRSA) strains, including strain COL, in which the high methicillin MIC for cultures grown at 37°C (800 µg/ml) was reduced to 12 µg/ml at 42°C. COL grew faster at 42°C than at 37°C and at the higher temperature produced cell walls of abnormal composition: there was an over-representation of the monomeric muropeptide without the oligoglycine chain and an increase in the representation of multimers that contained this wall component as the donor molecule. Screening of a Tn551 insertional library for mutants, in which the high and homogenous β-lactam antibiotic resistance of strain COL is retained at 42°C, identified mutant C245, which expressed high-level methicillin resistance and produced a cell wall of normal composition independent of the temperature. The Tn551 inactivated gene was found, by homology search, to encode for a sodium-dependent symporter, homologues of which are ubiquitous in both prokaryotic and eukaryotic genomes. Inactivation of this putative symporter in several heteroresistant clinical MRSA isolates caused striking increases in the level of their β-lactam resistance.


* Corresponding author. Mailing address: The Rockefeller University, Laboratory of Microbiology, 1230 York Ave., New York, NY 10021. Phone: (212) 327-8277. Fax: (212) 327-8688. E-mail: tomasz{at}rockefeller.edu

{triangledown} Published ahead of print on 3 December 2007.


Antimicrobial Agents and Chemotherapy, February 2008, p. 505-512, Vol. 52, No. 2
0066-4804/08/$08.00+0     doi:10.1128/AAC.00504-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.







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