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Antimicrobial Agents and Chemotherapy, October 2002, p. 3151-3155, Vol. 46, No. 10
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.10.3151-3155.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Carboxyl Terminus of Peptidoglycan Stem Peptides Is a Determinant for Methicillin Resistance in Staphylococcus aureus

Boudewijn L. M. de Jonge,1* Douglas Gage,,2,{dagger} and Naxing Xu2,{ddagger}

Laboratory of Microbiology, The Rockefeller University, New York, New York 10021,1 Department of Biochemistry, Michigan State University-National Institutes of Health Mass Spectrometry Facility, East Lansing, Michigan 488242

Received 26 December 2001/ Returned for modification 11 March 2002/ Accepted 26 June 2002

A mecA-containing Staphylococcus aureus strain was grown in the presence of high concentrations of D-serine, D-threonine, and D-phenylalanine. These growth conditions resulted in the replacement of the carboxyl-terminal (fifth) D-alanine residue of peptidoglycan stem peptides with the D-amino acid present in the growth medium and a reduced ability to grow in the presence of methicillin. The most dramatic effect was seen with D-serine. With 32 mM D-serine, strains that had been able to grow in the presence of 800 µg of methicillin per ml were only able to grow in the presence of less than 50 µg/ml. The results also suggest that in S. aureus vancomycin resistance mediated through the incorporation of precursors not terminating in D-alanyl-D-alanine would be mutually exclusive with expression of mecA-mediated methicillin resistance.

* Corresponding author. Present address: AstraZeneca R&D Boston, 35 Gatehouse Dr., Waltham, MA 02451. Phone: (781) 839-4535. Fax: (781) 839-4500. E-mail: boudewijn.dejonge{at}astrazeneca.com.

{dagger} Present address: Pfizer Global R&D, Ann Arbor, MI 48105.

{ddagger} Present address: Abbott Laboratories, Abbott Park, IL 60064.

Antimicrobial Agents and Chemotherapy, October 2002, p. 3151-3155, Vol. 46, No. 10
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.10.3151-3155.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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