Msr(A) and related macrolide/streptogramin resistance determinants: incomplete transporters?

The gene msr(A) confers inducible resistance to 14-membered-ring macrolides and type B streptogramins (MS(B) resistance) in staphylococci. The encoded hydrophilic protein (Msr(A)) is 488 amino acids and contains two ATP-binding motifs characteristic of the ABC transporters. The classical organisation of ABC transporters requires interaction between the two cytoplasmically located ATP-binding domains with two hydrophobic domains positioned in the membrane. Msr(A) appears to mediate drug efflux and yet contains no hydrophobic membrane spanning domains. In addition, Msr(A) functions in previously sensitive heterologous hosts such as Staphylococcus aureus in the absence of other plasmid encoded products. Current research on Msr(A) and related determinants in Gram-positive cocci and in antibiotic producing organisms is reviewed. Alternative hypotheses for the mechanism of action of Msr(A) (i.e. active transport vs. ribosomal protection) are discussed. Evidence indicating Msr(A) may have a role in virulence in addition to conferring antibiotic resistance is also considered.