Minami M, Kamimura T, Isaka M, Tatsuno I, Ohta M, Hasegawa T
Clindamycin-induced CovS-mediated regulation of the production of the virulent exoproteins streptolysin O, NAD glycohydrolase, and streptokinase in Streptococcus pyogenes. [JOURNAL ARTICLE]
Antimicrob Agents Chemother 2009 Oct 5.
The administration of high-dose clindamycin (CLI) along with penicillin is recommended for the treatment of streptococcal toxic shock syndrome. However, the prevalence of CLI-resistant Streptococcus pyogenes is increasing worldwide, and the effect of CLI on CLI-resistant S. pyogenes remains unknown. We aimed to evaluate the effect of CLI on the in vitro production of 3 major virulent exoproteins, namely, streptolysin O (Slo), NAD-glycohydrolase (Nga), and streptokinase (Ska), by CLI-resistant S. pyogenes. After incubation of M1 serotype CLI-resistant S. pyogenes D2TY in the presence of 1 mug/mL CLI, the amounts of Slo, Nga, and Ska and the mRNA levels of slo, nga, and ska in the supernatant were analyzed by northern blotting and western blotting respectively. The results of both assays showed that the production of Slo, Nga, and Ska was higher with CLI treatment than without CLI treatment. We evaluated the role of the sensor kinase CovS, which is involved in the two-component system of S. pyogenes, in the CLI-induced production of these 3 exoproteins. Northern blotting analysis revealed that CLI induced the expression of covS mRNA in the wild-type D2TY strain. Furthermore, both northern blotting and western blotting analysis showed that CLI decreased the expression of Slo, Nga, and Ska in the isogenic covS mutant D2TYcovS. These results suggest that CLI increases the production of 3 virulent exoproteins in CLI-resistant S. pyogenes via the action of CovS.
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