Inducible Erythromycin Resistance in Staphylococci Is Encoded by a Member of the ATP-binding Transport Super-Gene Family

Mol Microbiol. 1990 Jul;4(7):1207-14. doi: 10.1111/j.1365-2958.1990.tb00696.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Amino Acid Sequence
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Biological Transport
  • Drug Resistance, Microbial / genetics
  • Erythromycin / pharmacology*
  • Gene Expression Regulation, Bacterial
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Multigene Family*
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / genetics*

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • msrA protein, Staphylococcus epidermidis
  • Erythromycin
  • Adenosine Triphosphate

Associated data

  • GENBANK/X52085