An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin.
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 > or =40-fold decrease in MICs of Q-D (to 0.75 microg/ml), CLI (to 0.12 to 0.5 microg/ml), and dalfopristin (DAL) (to 4 to 8 microg/ml) for the wild-type E. faecalis parental strain (Q-D MIC, 32 microg/ml; CLI MIC, 32 to 48 microg/ml; DAL MIC, 512 microg/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 microg/ml) and had DAL MICs of 4 to 16 microg/ml; for the remaining erm(B)-lacking E. faecium strains, the CLI and DAL MICs were 4 to > 256 and 2 to > 128 microg/ml, respectively. In contrast, none of 32 erm(B)-lacking E. faecalis strains were susceptible (CLI MIC range, 16 to 32 microg/ml; DAL MIC range, > or =32 microg/ml). When lsa was introduced into an E. faecium strain initially susceptible to CLI, the MICs of CLI and DAL increased > or =60-fold and that of Q-D increased 6-fold (to 3 to 6 microg/ml). Introduction of lsa into two DAL-resistant (MICs, > 128 microg/ml), Q-D-susceptible (MICs, 0.5 and 1.5 microg/ml) E. faecium strains (CLI MICs, 12 and >256 microg/ml) resulted in an increase in the Q-D MICs from 3- to 10-fold (to 8 and >32 microg/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.
Singh
Kavindra V
KV
Center for the Study of Emerging and Reemerging Pathogens, Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Medical School at Houston, 77030, USA.
Weinstock
George M
GM
Murray
Barbara E
BE
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002981:Clindamycin / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000235:genetics*; D005798:Genes, Bacterial / Q000187:drug effects / Q000235:genetics*; D005816:Genetic Complementation Test; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014769:Virginiamycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D002981:Clindamycin