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
Ds. Kernodle et al., 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 Journal of infectious diseases, 172(2), 1995, pp. 410-419
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.