Abstract
Extracellular protein toxins contribute to the pathogenesis of a wide variety of Staphylococcus aureus infections. The present study investigated the effects that cell-wall active antibiotics and protein-synthesis inhibitors have on transcription and translation of genes for Panton-Valentine leukocidin, alpha-hemolysin, and toxic-shock syndrome toxin 1, in both methicillin-sensitive and methicillin-resistant S. aureus. Subinhibitory concentrations of nafcillin induced and prolonged mRNA for Panton-Valentine leukocidin, alpha-toxin, and toxic-shock syndrome toxin 1 and increased toxin production. In contrast, clindamycin and linezolid markedly suppressed translation, but not transcription, of toxin genes. These results suggest (1) that protein-synthesis inhibition is an important consideration in the selection of antimicrobial agents to treat serious infections caused by toxin-producing gram-positive pathogens and (2) that, by inducing and enhancing toxin production, inadvertent use of beta-lactam antibiotics to treat methicillin-resistant S. aureus infections may contribute to worse outcomes.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetamides / pharmacology
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Animals
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Anti-Bacterial Agents / pharmacology*
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Bacterial Toxins / biosynthesis
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Bacterial Toxins / genetics
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Clindamycin / pharmacology
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Enterotoxins / biosynthesis
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Enterotoxins / genetics
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Exotoxins / biosynthesis*
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Exotoxins / genetics
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Hemolysin Proteins / biosynthesis
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Hemolysin Proteins / drug effects
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Hemolysin Proteins / genetics
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Leukocidins / biosynthesis
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Leukocidins / genetics
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Linezolid
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Methicillin / pharmacology
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Methicillin Resistance*
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Microbial Sensitivity Tests
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Nafcillin / pharmacology
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Oxazolidinones / pharmacology
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Protein Synthesis Inhibitors / pharmacology*
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Rabbits
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / growth & development
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Staphylococcus aureus / pathogenicity*
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Superantigens / biosynthesis
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Superantigens / drug effects
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Superantigens / genetics
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Vancomycin / pharmacology
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Virulence
Substances
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Acetamides
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Anti-Bacterial Agents
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Bacterial Toxins
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Enterotoxins
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Exotoxins
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Hemolysin Proteins
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Leukocidins
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Oxazolidinones
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Panton-Valentine leukocidin
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Protein Synthesis Inhibitors
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Superantigens
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enterotoxin F, Staphylococcal
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Clindamycin
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Nafcillin
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Vancomycin
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Linezolid
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Methicillin