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

Elinor Reynolds1, Jeremy I Ross, Jonathan H Cove

  • 1Division of Microbiology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.

Insights

The msr(A) gene provides resistance to macrolides and streptogramins in staphylococci by encoding a unique ABC transporter protein. This protein mediates drug efflux without typical membrane domains, suggesting novel resistance mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • The msr(A) gene confers inducible resistance to macrolides and streptogramins in staphylococci.
  • The Msr(A) protein, a 488-amino acid hydrophilic protein, contains ATP-binding motifs typical of ABC transporters.

Purpose of the Study:

  • To review current research on Msr(A) and related determinants in Gram-positive cocci and antibiotic-producing organisms.
  • To discuss alternative hypotheses for Msr(A) mechanism of action (active transport vs. ribosomal protection).
  • To consider Msr(A)'s potential role in virulence.

Main Methods:

  • Literature review of research on msr(A) and related resistance determinants.
  • Analysis of Msr(A) protein structure and known ABC transporter organization.
  • Discussion of experimental evidence regarding Msr(A) function and potential roles.

Main Results:

  • Msr(A) mediates drug efflux despite lacking hydrophobic membrane-spanning domains.
  • Msr(A) functions in heterologous hosts like Staphylococcus aureus without additional plasmid factors.
  • Evidence suggests Msr(A) may contribute to bacterial virulence.

Conclusions:

  • Msr(A) represents a unique ABC transporter involved in antibiotic resistance.
  • The mechanism of action for Msr(A) may differ from classical ABC transporters, potentially involving ribosomal protection.
  • Msr(A) warrants further investigation for its dual role in resistance and virulence.

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