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.