Biochemical and genetic basis of tetracycline resistance in Staphylococcus aureus.

Both the genetic and biochemical basis of tetracycline resistance in a number of staphylococcal strains was investigated. The strains examined could be classified into three groups: (i) those possessing a high basal level of resistance and in which resistance could be induced to higher levels (macro-inducible); (ii) those which had a high uninduced level of resistance, but which were virtually uninducible (macro-constitutive); (iii) one derivative which had a low basal level of resistance and was also uninducible (micro-constitutive). Resistance in macro-constitutive strains was plasmid mediated and typical of organisms possessing wild-type plasmids. The macro-constitutive pattern of resistance appeared to be correlated with a chromosomal location for the resistance genes, whereas the micro-constitutive pattern was correlated with loss of a region from the wild-type plasmid. Analysis of membrane proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis suggested that a number of membrane polypeptides became unstable in staphylococci possessing high-level tetracycline resistance. In particular, the absence of a polypeptide of 22,000 daltons was always associated with high-level resistance. There was no evidence that multiple gene copies are required for expression of tetracycline resistance in Staphylococcus aureus.