This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Severin, A. Articles by Tomasz, A. Search for Related Content PubMed PubMed Citation Articles by Severin, A. Articles by Tomasz, A.

High-Level ß-Lactam Resistance and Cell Wall Synthesis Catalyzed by the mecA Homologue of Staphylococcus sciuri Introduced into Staphylococcus aureus

Anatoly Severin,^1, Shang Wei Wu,¹ Keiko Tabei,² and Alexander Tomasz^1*

Laboratory of Microbiology, The Rockefeller University, New York, New York 10021,¹ Wyeth Research, 401 N. Middletown Rd., Pearl River, New York 10965²

Received 5 May 2005/ Accepted 5 July 2005

A close homologue of mecA, the determinant of broad-spectrum ß-lactam resistance in Staphylococcus aureus was recently identified as a native gene in the animal commensal species Staphylococcus sciuri. Introduction of the mecA homologue from a methicillin-resistant strain of S. sciuri into a susceptible strain of S. aureus caused an increase in drug resistance and allowed continued growth and cell wall synthesis of the bacteria in the presence of high concentrations of antibiotic. We determined the muropeptide composition of the S. sciuri cell wall by using a combination of high-performance liquid chromatography, mass spectrometric analysis, and Edman degradation. Several major differences between the cell walls of S. aureus and S. sciuri were noted. The pentapeptide branches in S. sciuri were composed of one alanine and four glycine residues in contrast to the pentaglycine units in S. aureus. The S. sciuri wall but not the wall of S. aureus contained tri- and tetrapeptide units, suggesting the presence of DD- and LD-carboxypeptidase activity. Most interestingly, S. aureus carrying the S. sciuri mecA and growing in methicillin-containing medium produced a cell wall typical of S. aureus and not S. sciuri, in spite of the fact that wall synthesis under these conditions had an absolute dependence on the heterologous S. sciuri gene product. The protein product of the S. sciuri mecA can efficiently participate in cell wall biosynthesis and build a cell wall using the cell wall precursors characteristic of the S. aureus host.

Present address: Wyeth Research, 401 N. Middletown Rd., Pearl River, NY 10965.

This article has been cited by other articles:

• Zhou, Y., Antignac, A., Wu, S. W., Tomasz, A. (2008). Penicillin-Binding Proteins and Cell Wall Composition in -Lactam-Sensitive and -Resistant Strains of Staphylococcus sciuri. J. Bacteriol. 190: 508-514 [Abstract] [Full Text]