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The ABCF family protein Msr(A) confers high resistance to macrolides but only low resistance to ketolides in staphylococci. Mutations in conserved functional regions of ClpX as well as deletion ofclpX significantly increased Msr(A)-mediated resistance to the ketolide antibiotic telithromycin. ClpX is the chaperone component of the ClpXP two-component proteolytic system. Nevertheless, no changes in resistance were observed in aclpP knockout strain expressingmsr (A), demonstrating that ClpX affects Msr(A) independently of ClpP.

ClpP-Independent Function of ClpX Interferes with Telithromycin Resistance Conferred by Msr(A) in Staphylococcus aureus