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An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin - PubMed (original) (raw)

An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin

Kavindra V Singh et al. Antimicrob Agents Chemother. 2002 Jun.

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 > 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.

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Figures

FIG. 1.

FIG. 1.

Multiple-sequence alignment of Lsa, Msr(A), Msr(C), Vga(A), Vga(B), and YjcA. ClustalW, at the Baylor College of Medicine website, was used, and the GeneDoc software was used for editing and shading. Shown are the two ATP-binding domains, consisting of Walker A and B motifs (underlined) and an SGG sequence (underlined). The bottom line shows the consensus sequence. Regions in which the six proteins are 100% identical are marked in solid black, dark gray shows regions >80% identical, and light gray shows regions with >60% identical amino acids.

FIG. 1.

FIG. 1.

Multiple-sequence alignment of Lsa, Msr(A), Msr(C), Vga(A), Vga(B), and YjcA. ClustalW, at the Baylor College of Medicine website, was used, and the GeneDoc software was used for editing and shading. Shown are the two ATP-binding domains, consisting of Walker A and B motifs (underlined) and an SGG sequence (underlined). The bottom line shows the consensus sequence. Regions in which the six proteins are 100% identical are marked in solid black, dark gray shows regions >80% identical, and light gray shows regions with >60% identical amino acids.

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