GROWTH OF STAPHYLOCOCCUS-AUREUS WITH NAFCILLIN IN-VITRO INDUCES ALPHA-TOXIN PRODUCTION AND INCREASES THE LETHAL ACTIVITY OF STERILE BROTH FILTRATES IN A MURINE MODEL

The morbidity and mortality of Staphylococcus aureus infections remain high despite antibiotic therapy. To investigate further the observati on that penicillins increase the hemolytic activity of staphylococcal cultures, 37 strains mere grown in broth with and without subinhibitor y nafcillin. Nafcillin stimulated hemolytic activity in nafcillin-susc eptible and -resistant isolates. Sterile broth filtrates of nafcillin- associated cultures injected intraperitoneally in mice were more rapid ly lethal than filtrates of the same strain grown without nafcillin, L ethality was neutralized by anti-alpha-toxin antisera, DNA-RNA hybridi zation revealed a nafcillin-associated increase in alpha-toxin mRNA du ring the postexponential growth phase after the activation of agr. Iso lates grown in slightly inhibitory nafcillin concentrations had more a lpha-toxin mRNA than did nafcillin-free cultures, whereas agr RNAIII l evels were comparable, This suggests that nafcillin-induced alpha-toxi n production is not entirely attributable to agr. A supplemental regul atory mechanism may be involved.