Suppression of Intrinsic Resistance to Methicillin and Other Penicillins in Staphylococcus aureus

Abstract

The p H of the medium in which staphylococcal susceptibility to penicillins was determined was found to make a profound difference (128- to 8,000-fold) in the expression of “intrinsic” resistance, whereas β-lactamase-mediated resistance was only slightly affected by p H; methicillin-resistant staphylococci that are β-lactamase-negative are models of pure intrinsic resistance, and the common β-lactamase-producing organisms (methicillin-susceptible) are examples of pure β-lactamase-mediated resistance. Methicillin-resistant staphylococci were unable to express their resistance at p H 5.2. However, growth of methicillin-resistant organisms in acid ( p H 5.2) medium, followed by susceptibility testing at p H 7.4, showed no elimination of the genotype for intrinsic resistance, indicating that the p H effect was due to suppression, rather than to elimination of the gene determining the intrinsic resistance. These p H changes had little effect on the susceptibility of staphylococci that possessed neither intrinsic resistance nor β-lactamase-mediated resistance. Thus, the suppression of “intrinsic” resistance was highly specific, and probably not the result of a change in ionization of the antibiotic, which would have been expected to affect all cells essentially equally. It is unlikely that foci of inflammation in man become sufficiently acid to suppress methicillin resistance of the staphylococci causing infection and inflammation.