Modulation of protein A formation in Staphylococcus aureus by genetic determinants for methicillin resistance.

Many methicillin-resistant (Mec(r)) strains of Staphylococcus aureus either produce no protein A or secrete it extracellularly (S. Winblad and C. Ericson, Acta Pathol. Microbiol. Scand. Sect. B 81:150-156, 1973). We found that methicillin resistance and protein A production were apparently lost coordinately from the natively Mec(r) strain A676. Restoration of the genetic determinant for methicillin resistance (mec) by transduction or transformation restored protein A production. In two other Mec(r) strains, loss of mec was accompanied by marked reduction in protein A formation. Genetic transfer of mec to derivatives of S. aureus 8325 affected protein A formation differently with different mec determinants. Those derived from strain A676 and two other Mec(r) strains reduced the scanty amount of protein A produced by strain 8325 to even lower or undetectable levels, whereas mec from two more Mec(r) 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 and mec determinant, was reduced in methicillin-susceptible (Mec(s)) mutants produced by ethyl methane sulfonate treatment of Mec(r) strains. The mec-effect reappeared in spontaneous revertants to methicillin resistance. Phenotypic reduction of methicillin resistance in Mec(r) strains grown at 44 degrees C was accompanied by reduction of the mec-effect on protein A, but it had no effect on protein A formation in Mec(s) strains. Two independent mutants of strain 8325 produced large amounts of protein A at rates that were unaffected by growth at 44 degrees C or by the introduction of mec determinants.