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Suppression of intrinsic resistance to methicillin and other penicillins in Staphylococcus aureus
Abstract:
The pH 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 beta-lactamase-mediated resistance was only slightly affected by pH; methicillin-resistant staphylococci that are beta-lactamase-negative are models of pure intrinsic resistance, and the common beta-lactamase-producing organisms (methicillin-susceptible) are examples of pure beta-lactamase-mediated resistance. Methicillin-resistant staphylococci were unable to express their resistance at pH 5.2. However, growth of methicillin-resistant organisms in acid (pH 5.2) medium, followed by susceptibility testing at pH 7.4, showed no elimination of the genotype for intrinsic resistance, indicating that the pH effect was due to suppression, rather than to elimination of the gene determining the intrinsic resistance. These pH changes had little effect on the susceptibility of staphylococci that possessed neither intrinsic resistance nor beta-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.
Insights
The pH of growth medium significantly impacts staphylococcal penicillin resistance. Acidic conditions suppress intrinsic resistance in methicillin-resistant staphylococci, but do not alter the underlying genes.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Staphylococcal resistance to penicillins is a significant clinical concern.
- Two primary mechanisms of resistance exist: intrinsic resistance and beta-lactamase-mediated resistance.
- Understanding factors influencing resistance expression is crucial for effective treatment.
Purpose of the Study:
- To investigate the effect of medium pH on the expression of intrinsic and beta-lactamase-mediated staphylococcal resistance.
- To determine if pH-induced suppression of resistance involves genetic alteration or reversible gene expression.
Main Methods:
- Staphylococcal susceptibility testing to penicillins was performed across a range of pH values.
- Methicillin-resistant and methicillin-susceptible strains, with and without beta-lactamase production, were utilized.
- Comparative analysis of resistance expression at acidic (pH 5.2) and neutral (pH 7.4) conditions.
Main Results:
- Medium pH profoundly affected intrinsic resistance (128- to 8,000-fold change), while beta-lactamase-mediated resistance was only slightly affected.
- Methicillin-resistant staphylococci failed to express resistance at pH 5.2.
- Exposure to acidic conditions followed by testing at neutral pH demonstrated reversible suppression, not elimination, of intrinsic resistance genes.
Conclusions:
- The expression of intrinsic staphylococcal resistance is highly sensitive to medium pH, with acidic environments causing significant suppression.
- pH-mediated suppression of intrinsic resistance is a reversible phenomenon, not involving permanent genetic changes.
- The findings suggest that localized acidic environments in human infections are unlikely to sufficiently suppress methicillin resistance.