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Journal of Bacteriology, September 2006, p. 6286-6297, Vol. 188, No. 17
0021-9193/06/$08.00+0     doi:10.1128/JB.00457-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus Mutants with Increased Lysostaphin Resistance

Angelika Gründling, Dominique M. Missiakas, and Olaf Schneewind^*

Department of Microbiology, University of Chicago, Chicago, Illinois 60637

Received 3 April 2006/ Accepted 16 June 2006

Staphylococcus simulans secretes lysostaphin, a bacteriolytic enzyme that specifically binds to the cell wall envelope of Staphylococcus aureus and cleaves the pentaglycine cross bridges of peptidoglycan, thereby killing staphylococci. The study of S. aureus mutants with resistance to lysostaphin-mediated killing has revealed biosynthetic pathways for cell wall assembly. To identify additional genes involved in cell wall envelope biosynthesis, we have screened a collection of S. aureus strain Newman transposon mutants for lysostaphin resistance. Bursa aurealis insertion in SAV2335, encoding a polytopic membrane protein with predicted protease domain, caused a high degree of lysostaphin resistance, similar to the case for a previously described femAB promoter mutant. In contrast to the case for this femAB mutant, transposon insertion in SAV2335, herein named lyrA (lysostaphin resistance A), did not cause gross alterations of cell wall cross bridges such as truncations of pentaglycine to tri- or monoglycine. Also, inactivation of LyrA in a methicillin-resistant S. aureus strain did not precipitate a decrease in ß-lactam resistance as observed for fem (factor essential for methicillin resistance) mutants. Lysostaphin bound to the cell wall envelopes of lyrA mutants in a manner similar to that for wild-type staphylococci. Lysostaphin resistance of lyrA mutants is attributable to altered cell wall envelope properties and may in part be due to increased abundance of altered cross bridges. Other lyr mutants with intermediate lysostaphin resistance carried bursa aurealis insertions in genes specifying GTP pyrophosphokinase or enzymes of the purine biosynthetic pathway.

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* Corresponding author. Mailing address: Department of Microbiology, 920 E 58th Street, Chicago, IL 60637. Phone: (773) 843-9060. Fax: (773) 834-8150. E-mail: oschnee{at}bsd.uchicago.edu.

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Journal of Bacteriology, September 2006, p. 6286-6297, Vol. 188, No. 17
0021-9193/06/$08.00+0     doi:10.1128/JB.00457-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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