Growth of Staphylococcus aureus with Nafcillin In Vitro Induces α-Toxin Production and Increases the Lethal Activity of Sterile Broth Filtrates in a Murine Model

• Published in: The Journal of infectious diseases Vol. 172; no. 2; pp. 410 - 419
• Main Authors: Kernodle, Douglas S., McGraw, Patricia A., Barg, Neil L., Menzies, Barbara E., Voladri, Rama K. R., Harshman, Sidney
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.08.1995; University of Chicago Press
• Subjects: Animals; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiserum; beta-Lactamases - biosynthesis; beta-Lactamases - genetics; Biological and medical sciences; Coagulase - biosynthesis; Coagulase - genetics; Culture Media; Drug Resistance, Microbial; Endocarditis; Gene Expression Regulation, Bacterial; Hemolysin Proteins - biosynthesis; Hemolysin Proteins - genetics; Infections; Major Articles; Male; Medical sciences; Messenger RNA; Mice; Nafcillin - pharmacology; Neutralization Tests; Penicillin; Pharmacology. Drug treatments; Phosphoric Monoester Hydrolases - biosynthesis; Phosphoric Monoester Hydrolases - genetics; RNA; RNA, Bacterial - analysis; RNA, Messenger - genetics; Staphylococcal Infections - microbiology; Staphylococcal Infections - mortality; Staphylococcus; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - metabolism; Staphylococcus aureus - pathogenicity; Survival Rate; Toxins; Type C Phospholipases - biosynthesis; Type C Phospholipases - genetics; Staphylococcus aureus; Growth; Rodentia; In vitro; Biological activity; Penicillin derivatives; Toxin; Vertebrata; Mammalia; Mouse; Animal; Production; Bacteria; Micrococcales; Micrococcaceae; Antibacterial agent; Staphylococcus aureus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/172.2.410

The morbidity and mortality of Staphylococcus aureus infections remain high despite antibiotic therapy. To investigate further the observation that penicillins increase the hemolytic activity of staphylococcal cultures, 37 strains were grown in broth with and without subinhibitory nafcillin. Nafcillin stimulated hemolytic activity in nafcillin-susceptible and -resistant isolates. Sterile broth filtrates of nafcillin-associated cultures injected intraperitoneally in mice were more rapidly lethal than filtrates of the same strain grown without nafcillin. Lethality was neutralized by anti-α-toxin antisera. DNA-RNA hybridization revealed a nafcillin-associated increase in α-toxin mRNA during the postexponential growth phase after the activation of agr. Isolates grown in slightly inhibitory nafcillin concentrations had more α-toxin mRNA than did nafcillin-free cultures, whereas agr RNAIII levels were comparable. This suggests that nafcillin-induced α-toxin production is not entirely attributable to agr. A supplemental regulatory mechanism may be involved.