Singh Kavindra V, Weinstock George M, Murray Barbara E
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.
Antimicrob Agents Chemother. 2002 Jun;46(6):1845-50. doi: 10.1128/AAC.46.6.1845-1850.2002.
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 > 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.
粪肠球菌分离株对克林霉素（CLI）和奎奴普丁 - 达福普汀（Q - D）耐药，这被认为是该菌种的一个特征。粪肠球菌的一个基因（abc - 23，现命名为lsa，代表“林可酰胺和链阳菌素A耐药”）的破坏与野生型粪肠球菌亲本菌株对Q - D（降至0.75微克/毫升）、CLI（降至0.12至0.5微克/毫升）和达福普汀（DAL）（降至4至8微克/毫升）的最低抑菌浓度（MIC）降低≥40倍有关（Q - D的MIC为32微克/毫升；CLI的MIC为32至48微克/毫升；DAL的MIC为512微克/毫升）。用穿梭质粒上的lsa对破坏突变体进行互补，导致CLI、Q - D和DAL的MIC恢复到野生型水平。在高严格条件下，在180株粪肠球菌分离株中均发现了lsa，但在189株其他肠球菌中均未发现。在19株缺乏erm(B)的屎肠球菌菌株中，9株（47%）对CLI高度敏感（MIC为0.06至0.25微克/毫升），DAL的MIC为4至16微克/毫升；对于其余缺乏erm(B)的屎肠球菌菌株，CLI和DAL的MIC分别为4至>256微克/毫升和2至>128微克/毫升。相比之下，32株缺乏erm(B)的粪肠球菌菌株均无敏感性（CLI的MIC范围为16至32微克/毫升；DAL的MIC范围≥32微克/毫升）。当将lsa引入最初对CLI敏感的屎肠球菌菌株时，CLI和DAL的MIC增加≥60倍，Q - D的MIC增加6倍（至3至6微克/毫升）。将lsa引入两株对DAL耐药（MIC>128微克/毫升）、对Q - D敏感（MIC为0.5和1.5微克/毫升）的屎肠球菌菌株（CLI的MIC为12和>256微克/毫升），导致Q - D的MIC分别增加3至10倍（至8和>32微克/毫升）。虽然未研究外排情况，但预测的Lsa蛋白与金黄色葡萄球菌的Vga(A)、Vga(B)和Msr(A)以及乳酸乳球菌的YjcA等ABC蛋白的相似性（41%至64%）以及沃克A和B ATP结合基序的存在表明，这种耐药性可能与这些抗生素的外排有关。总之，lsa似乎是粪肠球菌的一个固有基因，它解释了该菌种对CLI和Q - D的特征性耐药性。
