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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.
Abstract:
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.
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.