AAC Accepts, published online ahead of print on 13 November 2006

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Antimicrob. Agents Chemother. doi:10.1128/AAC.00539-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Growth phase dependent effect of clindamycin on the production of exoproteins by Streptococcus pyogenes

Jun Sawai, Tadao Hasegawa^*, Takuya Kamimura, Akira Okamoto, Daisuke Ohmori, Nobuyuki Nosaka, Keiko Yamada, Keizo Torii, and Michio Ohta

Department of Molecular Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan, Department of Bacteriology, Nagoya City University School of Medical Sciences, 1 Kawasumi Mizuho-cho Mizuho-ku, Nagoya 467-8601, Japan

^* To whom correspondence should be addressed. Email: tadaoh{at}med.nagoya-cu.ac.jp,

The administration of high-dose clindamycin plus benzylpenicillin has been recommended for the treatment of streptococcal toxic shock-like syndrome caused by Streptococcus pyogenes and clindamycin has been found to be more effective than beta-lactams in retrospective analysis of human cases. Although therapeutic doses of clindamycin have been also shown to be effective in experimental infections and clindamycin has great efficacy against the production of bacterial exoproteins, we recently reported that the level of production of some exoproteins was unchanged or even increased by a subinhibitory dose of clindamycin added upon initiation of bacterial culture, when treated cultures were analyzed by two-dimensional gel electrophoresis. In this study we further examined the effect of clindamycin on the production of exoproteins by adding it to Streptococcus pyogenes cultures during various growth phases. We found that the production of some proteins, NAD (+)-glycohydrolase, Streptolysin O, and Streptococcal inhibitor of complement, was increased when clindamycin was added at early log phase growth, results that were seen when clindamycin was added at the beginning of culture. However, clindamycin inhibited the production of most types of proteins when it was administered to Streptoccocus pyogenes cultures at mid log phase growth. In csrS or mga knockout bacterial strains, the increase of exoproteins seen in parental strains was considerably inhibited. Our study indicates that the in vitro effect of clindamycin on the production of exoproteins greatly depends on the growth phase of bacteria and some regulatory factors of S. pyogenes that are involved in this phenomenon.

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