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Antimicrobial Agents and Chemotherapy, January 2002, p. 75-81, Vol. 46, No. 1
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.46.1.75-81.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Increased Glycan Chain Length Distribution and Decreased Susceptibility to Moenomycin in a Vancomycin-Resistant Staphylococcus aureus Mutant
Hitoshi Komatsuzawa,1* Kouji Ohta,1 Sakuo Yamada,2 Kerstin Ehlert,3 Harald Labischinski,3 Junko Kajimura,1 Tamaki Fujiwara,1 and Motoyuki Sugai1
Department of Microbiology, Hiroshima University Faculty of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima City, Hiroshima 734-8553,1
Department of Microbiology, Kawasaki Medical School, Matsushima, Kurashiki, Okayama 701-0192, Japan,2
Bayer AG, PH-Research Antiinfectives III, D42096 Wuppertal, Germany3
Received 16 April 2001/
Returned for modification 29 August 2001/
Accepted 29 September 2001
A vancomycin-resistant Staphylococcus aureus mutant, COL-VR1 (MIC, 16 µg/ml), was isolated from methicillin-resistant S. aureus COL by exposure to vancomycin. COL-VR1 also showed decreased susceptibility to teicoplanin (8-fold), methicillin (2-fold), macarbomycin (8-fold), and moenomycin (16-fold). Macarbomycin and moenomycin are thought to directly inhibit transglycosylase activity. Characterization of the mutant revealed a thickened cell wall and suppression of penicillin-induced lysis, although the amounts of the five penicillin-binding proteins (PBPs 1, 2, 3, 4, and 2') and the profiles of peptidoglycan hydrolases were not altered. Analysis of muropeptide profile and glycan chain length distribution by reversed-phase high-pressure liquid chromatography revealed slightly decreased peptide cross-linking and an increased average glycan chain length compared to those of the parent. These results together suggest that a transglycosylase activity was enhanced in the mutant. This may represent a novel mechanism of glycopeptide resistance in S. aureus.
* Corresponding author. Mailing address: Department of Microbiology, Hiroshima University Faculty of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima City, Hiroshima 734-8553, Japan. Phone: 81 82 257 5636. Fax: 81 82 257 5639. E-mail: hkomatsu{at}ipc.hiroshima-u.ac.jp.
Antimicrobial Agents and Chemotherapy, January 2002, p. 75-81, Vol. 46, No. 1
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.46.1.75-81.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.