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

Abstract
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 analyses of human cases. Although therapeutic doses of clindamycin have also been shown to be effective against 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 when it is added upon the initiation of bacterial culture and the 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 levels of production of some proteins, NAD+ glycohydrolase, streptolysin O, and streptococcal inhibitor of complement, were increased when clindamycin was added at early-log-phase growth, which was the result that was 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 Streptococcus pyogenes cultures at mid-log-phase growth. In csrS- or mga-knockout bacterial strains, the increase in 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 Streptococcus pyogenes that are involved in this phenomenon.
AuthorsJun Sawai, Tadao Hasegawa, Takuya Kamimura, Akira Okamoto, Daisuke Ohmori, Nobuyuki Nosaka, Keiko Yamada, Keizo Torii, Michio Ohta
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 51 Issue 2 Pg. 461-7 (Feb 2007) ISSN: 0066-4804 [Print] United States
PMID17101685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Streptolysins
  • streptolysin O
  • Clindamycin
  • NAD+ Nucleosidase
Topics
  • Anti-Bacterial Agents (pharmacology)
  • Bacterial Proteins (biosynthesis)
  • Clindamycin (pharmacology)
  • Gene Expression Regulation, Bacterial (drug effects)
  • Humans
  • NAD+ Nucleosidase (biosynthesis)
  • Streptococcal Infections (drug therapy, microbiology)
  • Streptococcus pyogenes (drug effects, growth & development, metabolism)
  • Streptolysins (biosynthesis)

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