Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family.
A Staphylococcus epidermidis plasmid conferring inducible resistance to 14-membered ring macrolides and type B streptogramins has been analysed and the DNA sequence of the gene responsible for resistance determined. A single open reading frame of 1.464 kbp, preceded by a complex control region containing a promoter and two ribosomal binding sites, was identified. The deduced sequence of the 488-amino-acid protein (MsrA) revealed the presence of two ATP-binding motifs homologous to those of a family of transport-related proteins from Gram-negative bacteria and eukaryotic cells, including the P-glycoprotein responsible for multidrug resistance. In MsrA, but not these other proteins, the two potential ATP-binding domains are separated by a Q-linker of exceptional length. Q-linkers comprise a class of flexible interdomain fusion junctions that are typically rich in glutamine and other hydrophilic amino acids and have a characteristic spacing of hydrophobic amino acids, as found in the MsrA sequence. Unlike the other transport-related proteins, which act in concert with one or more hydrophobic membrane proteins, MsrA appears to function independently when cloned in a heterologous host (Staphylococcus aureus RN4220). MsrA might, therefore, interact with and confer antibiotic specificity upon other transmembrane efflux complexes of staphylococcal cells. The active efflux of [14C]-erythromycin from cells of S. aureus RN4220 containing msrA has been demonstrated.
Ross
J I
JI
Department of Microbiology, University of Leeds, UK.
Eady
E A
EA
Cove
J H
JH
Cunliffe
W J
WJ
Baumberg
S
S
Wootton
J C
JC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport; D004352:Drug Resistance, Microbial / Q000235:genetics; D004917:Erythromycin / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000235:genetics*
D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C066202:msrA protein, Staphylococcus epidermidis; D004917:Erythromycin; D000255:Adenosine Triphosphate