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Many methicillin-resistant (Mecr ) strains ofStaphylococcus aureus either produce no protein A or secrete it extracellularly (S. Winblad and C. Ericson, Acta Pathol. Microbiol. Scand. Sect. B81: 150–156, 1973). We found that methicillin resistance and protein A production were apparently lost coordinately from the natively Mecr strain A676. Restoration of the genetic determinant for methicillin resistance (mec ) by transduction or transformation restored protein A production. In two other Mecr strains, loss ofmec was accompanied by marked reduction in protein A formation. Genetic transfer ofmec to derivatives ofS. aureus 8325 affected protein A formation differently with differentmec determinants. Those derived from strain A676 and two other Mecr strains reduced the scanty amount of protein A produced by strain 8325 to even lower or undetectable levels, whereasmec from two more Mecr strains increased its protein A content. This “mec -effect,” i.e., stimulation or inhibition of protein A formation dependent on the combination of host strain andmec determinant, was reduced in methicillin-susceptible (Mecs ) mutants produced by ethyl methane sulfonate treatment of Mecr strains. Themec -effect reappeared in spontaneous revertants to methicillin resistance. Phenotypic reduction of methicillin resistance in Mecr strains grown at 44°C was accompanied by reduction of themec -effect on protein A, but it had no effect on protein A formation in Mecs strains. Two independent mutants of strain 8325 produced large amounts of protein A at rates that were unaffected by growth at 44°C or by the introduction ofmec determinants.

Modulation of Protein A Formation in Staphylococcus aureus by Genetic Determinants for Methicillin Resistance