Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus.
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.
Stevens
Dennis L
DL
Veterans Affairs Medical Center, Boise, ID 83702, USA. dlsteven@mindspring.com
Ma
Yongsheng
Y
Salmi
Daniel B
DB
McIndoo
Eric
E
Wallace
Randi J
RJ
Bryant
Amy E
AE
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics; D002981:Clindamycin / Q000494:pharmacology; D004768:Enterotoxins / Q000096:biosynthesis / Q000235:genetics; D005098:Exotoxins / Q000096:biosynthesis* / Q000235:genetics; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D007956:Leukocidins / Q000096:biosynthesis / Q000235:genetics; D000069349:Linezolid; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009254:Nafcillin / Q000494:pharmacology; D023303:Oxazolidinones / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D018089:Superantigens / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology; D014774:Virulence
D000081:Acetamides; D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007956:Leukocidins; D023303:Oxazolidinones; C078284:Panton-Valentine leukocidin; D011500:Protein Synthesis Inhibitors; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D002981:Clindamycin; D009254:Nafcillin; D014640:Vancomycin; D000069349:Linezolid; D008712:Methicillin