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Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus.

ABSTRACT: It has long been known that certain antibiotics, at subinhibitory concentrations, differentially inhibit the synthesis of alpha-hemolysin and other staphylococcal virulence factors. In this report, we show that subinhibitory clindamycin (SBCL) eliminates production of nearly all exoproteins by Staphylococcus aureus but has virtually no effect on cytoplasmic proteins. The effect 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 production of several of the individual exoprotein genes, including spa (encoding protein A), hla (encoding alpha-hemolysin), and spr (encoding serine protease), at the level of transcription, suggesting that the primary effect must be differential inhibition of the synthesis of one or more regulatory proteins. In contrast to earlier reports, however, we found that subinhibitory clindamycin stimulates synthesis of coagulase and fibronectin binding protein B, also at the level of transcription. agr and sar expression was minimally affected by subinhibitory clindamycin. These effects varied from strain to strain and do not seem to be responsible for the effects of subinhibitory clindamycin on the overall exoprotein pattern.

SUBMITTER: Herbert S

PROVIDER: S-EPMC98253 | biostudies-literature | 2001 May

REPOSITORIES: biostudies-literature

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Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus.

Herbert S S Barry P P Novick R P RP

Infection and immunity 20010501 5

It has long been known that certain antibiotics, at subinhibitory concentrations, differentially inhibit the synthesis of alpha-hemolysin and other staphylococcal virulence factors. In this report, we show that subinhibitory clindamycin (SBCL) eliminates production of nearly all exoproteins by Staphylococcus aureus but has virtually no effect on cytoplasmic proteins. The effect was abolished by a gene conferring resistance to macrolides-lincosamides-streptogramin B, showing that differential inh ...[more]

PMID: 11292717

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Project description:Osteomyelitis (OM) is a complicated and serious disease and its underlying molecular signatures of disease initiation and progression remain unclear. Staphylococcus aureus (S. aureus) is the most common causative agent of OM. Previous study of Banchereau et al. has established a link between whole blood transcription profiles and clinical manifestations in patients infected with S. aureus. However, the differentially expressed genes (DEGs) in OM induced by S. aureus infection have not been intensively investigated. In this study, we downloaded the gene expression profile dataset GSE30119 from Gene Expression Omnibus, and performed bioinformatic analysis to identify DEGs in S. aureus infection induced OM from the transcriptional level. The study consisted of 143 whole blood samples, including 44 healthy controls, 42 OM-free, and 57 OM infection patients. A total of 209 S. aureus infection-related genes (SARGs) and 377 OM-related genes (OMRGs) were identified. The SARGs were primarily involved in the immune response by GO functional and pathway enrichment analysis. Several proteins adhere to neutrophil extracellular traps may be critical for the immune response to the process of S. aureus infection. By contrast, the OMRGs differ from the SARGs. The OMRGs were enriched in transmembrane signaling receptor and calcium channel activity, cilium morphogenesis, chromatin silencing, even multicellular organism development. Several key proteins, including PHLPP2 and EGF, were hub nodes in protein-protein interaction network of the OMRGs. In addition, alcoholism, systemic lupus erythematosus and proteoglycans in cancer were the top pathways influenced by the OMRGs associated with OM. Thus, this study has further explored the DEGs and their biological functions associated with S. aureus infection and OM, comparing with the previous study, and may light the further insight into the underlying molecular mechanisms and the potential critical biomarkers in OM development.

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Dataset Information

Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus.

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Subinhibitory clindamycin differentially inhibits transcription of exoprotein genes in Staphylococcus aureus.

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