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

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Many methicillin-resistant (Mecr) 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 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 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 Mecr strains reduced the scanty amount of protein A produced by strain 8325 to even lower or undetectable levels, whereas mec 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 and mec determinant, was reduced in methicillin-susceptible (Mecs) mutants produced by ethyl methane sulfonate treatment of Mecr strains. The mec-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 the mec-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 of mec determinants.

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