Phenotypic Suppression of Methicillin Resistance in Staphylococcus aureus by Mutant Noninducible Penicillinase Plasmids

Abstract

Methicillin (intrinsic) resistance of Staphylococcus aureus was suppressed almost completely by regulatory gene (penIl) mutations of penicillinase plasmids that made penicillinase production strictly noninducible. Methicillin resistance was restored by secondary regulatory gene mutations that altered the noninducible phenotype or by complementation with a compatible plasmid that did not bear the noninducible mutation. No evidence was obtained for genetic linkage between a penicillinase plasmid and the gene for methicillin resistance. We suggest, therefore, that the mutant noninducible repressor acted in trans by binding to a site on the methicillin resistance determinant. This hypothesis would imply an appreciable degree of homology between penicillinase plasmids and methicillin resistance genes. 682 on July 16, 2020 by guest

Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications.

“…␤-Lactamase regulatory genes may affect the expression of resistance. Mutations altering the inducibility of ␤-lactamase have been associated with reduced (i.e., heterogeneous) expression of methicillin resistance (24). Inactivation of blaR1 can produce heterogeneous resistance, presumably by the unopposed repressor activity of BlaI (57).…”

Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes.

“…Either the physical binding of the penicillin itself or perhaps an effect of penicillin in inhibiting peptidoglycan synthesis leads to transfer of information to the cytoplasm and activation of penicillinase synthesis. Although the entire receptor-transmitter complex might be components of the penicillinase system, another possibility is that some genetic elements involved in control of cell wall synthesis may also be involved in regulation of penicillinase production (37,38).…”

Methicillin-resistant staphylococci.

“…For example, recipient effectiveness for transduction of mec requires the presence of either a chromosomal or a plasmid determinant for beta-lactamase production and efficiency of transfer is lower in the presence of beta-lactamase inhibitor (38,39,148). Expression of resistance can be suppressed by mutant-noninducible penicillinase plasmids (37). Recipient effectiveness for mec in Staphylococcus epidermidis partly depends on the presence of the determinant for mercury resistance (19).…”

“…Genetic determinants physically distinct from mec can alter expression of resistance. The first indication that markers not linked to mec could alter expres-sion of methicillin resistance came from the studies of Cohen and colleagues (37). They found that methicillin resistance could be suppressed by mutations in regulatory genes of inducible penicillinase plasmids.…”