Impact of Antibiotics on Expression of Virulence-Associated Exotoxin Genes in Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus

• Published in: The Journal of infectious diseases 2007-01, Vol.195 (2), p.202-211
• Main Authors: Stevens, Dennis L., Ma, Yongsheng, Salmi, Daniel B., McIndoo, Eric, Wallace, Randi J., Bryant, Amy E.
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bacterial Toxins - biosynthesis; Bacterial Toxins - genetics; Bacteriology; Biological and medical sciences; Clindamycin - pharmacology; Enterotoxins - biosynthesis; Enterotoxins - genetics; Exotoxins - biosynthesis; Exotoxins - genetics; Fundamental and applied biological sciences. Psychology; Hemolysin Proteins - biosynthesis; Hemolysin Proteins - drug effects; Hemolysin Proteins - genetics; Infections; Infectious diseases; Leukocidins; Leukocidins - biosynthesis; Leukocidins - genetics; Linezolid; Medical sciences; Messenger RNA; Methicillin - pharmacology; Methicillin Resistance; Methicillin resistant staphylococcus aureus; Microbial Sensitivity Tests; Microbiology; Miscellaneous; Nafcillin - pharmacology; Oxazolidinones - pharmacology; Protein Synthesis Inhibitors - pharmacology; Rabbits; Staphylococcus; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development; Staphylococcus aureus - pathogenicity; Superantigens - biosynthesis; Superantigens - drug effects; Superantigens - genetics; Toxicity; Toxins; Vancomycin - pharmacology; Virulence
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/510396

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