Inducible erythromycin resistance in staphlyococci is encoded by a member of the ATP‐binding transport super‐gene family
Abstract
Summary: 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 1.464kbp, 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 inter‐domain 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 [14 C]‐erythromycin from cells of S. aureus RN4220 containing msrA has been demonstrated.
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Macrolide resistance due to Mef pumps does not result in cross-resistance to lincosamides and streptogramins, the MLSB group.
“Importantly, macrolide resistance due to these pumps does not result in cross-resistance to lincosamides and streptogramins (the so called MLSB group) (50).”
From Mechanisms of Antibiotic Resistance (2016) · cites this paper as [50]
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- Authors
- Ross, J. I., Eady, E. A., Cove, J. H., Cunliffe, W. J., Baumberg, S., & Wootton, J. C.
- Affiliations
- University of Leeds (GB)
- Leeds General Infirmary (GB)
- Corresponding author
- Eady, E. A.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 1990-07
- Volume
- 4
- Issue
- 7
- Pages
- 1207-1214
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2074955119
- Cited by
- 358
- References
- 43
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 10 · 2022: 6 · 2021: 6 · 2020: 15 · 2019: 9 · 2018: 11 · 2017: 10 · 2016: 16 · 2015: 10 · 2014: 12 · 2013: 8 · 2012: 6
- FWCI
- 8.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- inducible antibiotic resistance, erythromycin resistance, Staphylococcus epidermidis, Staphylococcus aureus, macrolide resistance, MsrA, multidrug resistance, efflux pumps, plasmid-mediated resistance, gene sequence analysis
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Bacterial Proteins, Base Sequence, Biological Transport, Drug Resistance, Microbial, Erythromycin, Multigene Family, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Staphylococcus epidermidis, Restriction Mapping, Gene Expression Regulation, Bacterial, Membrane Transport Proteins
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