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Antimicrobial Agents and Chemotherapy, June 2002, p. 1845-1850, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1845-1850.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Kavindra V. Singh,1,2 George M. Weinstock,1,3,4 and Barbara E. Murray1,2,4*

Center for the Study of Emerging and Reemerging Pathogens,1 Division of Infectious Diseases, Department of Internal Medicine,2 Department of Microbiology and Molecular Genetics, The University of Texas Medical School at Houston,4 Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 770303

Received 24 October 2001/ Returned for modification 29 January 2002/ Accepted 21 March 2002

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.

* Corresponding author. Mailing address: Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Medical School—Houston, 6431 Fannin, 1.728 JFB, Houston, TX 77030. Phone: (713) 500-6767. Fax: (713) 500-6766. E-mail: bem.asst{at}uth.tmc.edu.

Antimicrobial Agents and Chemotherapy, June 2002, p. 1845-1850, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1845-1850.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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