Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus

It has long been known that certain antibiotics, tit subinhibitory concentr ations, differentially inhibit the synthesis of a-hemolysin and other staph ylococcal virulence factors. In this report, we show that subinhibitory cli ndamycin (SBCL) eliminates production of nearly all exoproteins by Staphylo coccus aureus but has virtually no effect on cytoplasmic proteins. The effe ct was abolished by a gene conferring resistance to macrolides-lincosamides -streptogramin B, showing that differential inhibition of protein synthesis is responsible; remarkably, however, subinhibitory clindamycin blocked pro duction of several of the individual exoprotein genes, including spa (encod ing protein A), hla (encoding alpha -hemolysin), and spr (encoding serine p rotease), at the level of transcription, suggesting that the primary effect must be differential inhibition of the synthesis of one or more reg ulator y proteins. In contrast to earlier reports, however, we found that subinhib itory: clindamycin in stimulates synthesis of coagulase and fibronectin bin ding protein B, also at the level of transcription, agr and sar expression was minimally affected by subinhibitory clindamycin cin. These effects vari ed from strain to strain and do not seem to be responsible for the effects of subinhibitory clindamycin on the overall exoprotein pattern.