Induction of staphylococcal β-lactamase in response to low concentrations of methicillin under simulated diving environments

Abstract

The influence of simulated diving environments on the antimicrobial activity of a variety of penicillin and cephalosporin congeners was studied in Staphylococcus aureus. Pressure reduced bacteriostatic action provided the antibiotic was susceptible to β-lactamase hydrolysis and the bacterium was inducible for penicillinase. Ethidium bromide curing of the penicillinase plasmid of an inducible strain eliminated the hyperbaric effect. The minimal inhibitory concentration of benzylpenicillin increased about threefold with increasing hyperbaric pressure from 17 to 136 atm. Additional pressurization to 204 atm did not change antibiotic efficacy further. The efficacy of benzylpenicillin was reduced by 68 atm of hyperbaric helium, nitrogen, or a mixture of neon and helium, but was slightly increased by 68 atm of argon, removal of the gas phase, or 68 atm of hydrostatic pressure. Hyperbaric helium had no effect on β-lactamase activity in vitro. An effect was demonstrated upon induction by suboptimal concentrations of methicillin. The concentration of methicillin required for the induction of half-maximal levels of penicillinase in late log cultures of S. aureus was reduced from 0.15 μg/ml at 1 atm to 0.06 μg/ml at 68 atm. The basis of increased resistance to antibiotics exhibited by S. aureus in hyperbaric environments appears to be enhanced efficiency of penicillinase induction.