Cited by 263Antibiotic Resistance in BacteriaAntimicrobial Resistance in StaphylococcusBacterial Genetics and Biotechnology

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An Enterococcus faecalis ABC Homologue (Lsa) Is Required for the Resistance of This Species to Clindamycin and Quinupristin-Dalfopristin

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Singh, Kavindra V., Weinstock, George M., Murray, Barbara E.·2002·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.46.6.1845-1850.2002PMC PMC127256

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Abstract

Enterococcus faecalis isolates are resistant to clindamycin (CLI) and quinupristin-dalfopristin (Q-D), and this is thought to be a species characteristic. Disruption of a gene ( abc-23 , now designated lsa , for “lincosamide and streptogramin A resistance”) of E. faecalis was associated with a ≥40-fold decrease in MICs of Q-D (to 0.75 μg/ml), CLI (to 0.12 to 0.5 μg/ml), and dalfopristin (DAL) (to 4 to 8 μg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 μg/ml; CLI MIC, 32 to 48 μg/ml; DAL MIC, 512 μg/ml). Complementation of the disruption mutant with lsa on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels. Under high-stringency conditions, lsa was found in 180 of 180 isolates of E. faecalis but in none of 189 other enterococci. Among 19 erm (B)-lacking Enterococcus faecium strains, 9 (47%) were highly susceptible to CLI (MIC, 0.06 to 0.25 μg/ml) and had DAL MICs of 4 to 16 μg/ml; for the remaining erm (B)-lacking E. faecium strains, the CLI and DAL MICs were 4 to >256 and 2 to >128 μg/ml, respectively. In contrast, none of 32 erm (B)-lacking E. faecalis strains were susceptible (CLI MIC range, 16 to 32 μg/ml; DAL MIC range, ≥32 μg/ml). When lsa was introduced into an E. faecium strain initially susceptible to CLI, the MICs of CLI and DAL increased ≥60-fold and that of Q-D increased 6-fold (to 3 to 6 μg/ml). Introduction of lsa into two DAL-resistant (MICs, >128 μg/ml), Q-D-susceptible (MICs, 0.5 and 1.5 μg/ml) E. faecium strains (CLI MICs, 12 and >256 μg/ml) resulted in an increase in the Q-D MICs from 3- to 10-fold (to 8 and >32 μg/ml), respectively. Although efflux was not studied, the similarity (41 to 64%) of the predicted Lsa protein to ABC proteins such as Vga(A), Vga(B), and Msr(A) of Staphylococcus aureus and YjcA of Lactococcus lactis and the presence of Walker A and B ATP-binding motifs suggest that this resistance may be related to efflux of these antibiotics. In conclusion, lsa appears to be an intrinsic gene of E. faecalis that explains the characteristic resistance of this species to CLI and Q-D.

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Authors: Singh, K. V., Weinstock, G. M., & Murray, B. E.
Affiliations: Center for the Study of Emerging and Reemerging Pathogens
Baylor College of Medicine (US)
The University of Texas Health Science Center at Houston (US)
Corresponding author: Murray, Barbara E.
ORCID: Singh, Kavindra V.
Weinstock, George M.
Murray, Barbara E.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2002-06
Volume: 46
Issue: 6
Pages: 1845-1850
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.46.6.1845-1850.2002
PMC: PMC127256
OpenAlex: W1980535030
Cited by: 263
References: 45
Citations by year: 2026: 11 · 2025: 9 · 2024: 16 · 2023: 17 · 2022: 19 · 2021: 15 · 2020: 15 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 16 · 2015: 9 · 2014: 10 · 2013: 10 · 2012: 4
FWCI: 7.05
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
U.S. Public Health Service
National Institute of Allergy and Infectious Diseases (R37AI047923, AI 47923, R01AI047923)
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Topics: Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: Enterococcus faecalis, ABC transporters, clindamycin resistance, quinupristin-dalfopristin resistance, Enterococcus faecium, ermB gene, antibiotic resistance genes
MeSH terms: Amino Acid Sequence, Anti-Bacterial Agents, Clindamycin, DNA, Bacterial, Drug Resistance, Drug Therapy, Combination, Genes, Bacterial, Genetic Complementation Test, Microbial Sensitivity Tests, Molecular Sequence Data, Enterococcus faecalis, Virginiamycin, Reverse Transcriptase Polymerase Chain Reaction

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An Enterococcus faecalis ABC Homologue (Lsa) Is Required for the Resistance of This Species to Clindamycin and Quinupristin-Dalfopristin

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