Stability, persistence, and evolution of plasmid-encoded VanA glycopeptide resistance in enterococci in the absence of antibiotic selection in vitro and in gnotobiotic mice
Stability, persistence, and evolution of plasmid-encoded VanA glycopeptide resistance in enterococci in the absence of antibiotic selection in vitro and in gnotobiotic mice
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DOI：
10.1089/107662902760326869
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发表时间：
2002-09-01
影响因子：
2.6
通讯作者：
Sundsfjord, A
中科院分区：
文献类型：
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作者：
Johnsen, PJ;Simonsen, GS;Sundsfjord, A
在缺乏抗生素选择的情况下，已经观察到瓦那糖肽耐药肠球菌(GRE)的长期存在。在本研究中，我们检测了一株糖肽敏感的屎肠球菌亲本菌株及其质粒介导的Vana抗性衍生菌株在连续转移肉汤培养中1000代前后的适应度参数，无论是否有抗生素选择。除了含有VANA的质粒外，其他菌株都是同源的。此外，我们还研究了VANA抗性决定簇在体外和小鼠体内的稳定性。竞争实验表明，与敏感亲本相比，具有新获得的Vana抗性的GRE的适合度降低了4%。抗性品系和感病品系之间的竞争适合度的相对差异在1000代后没有显著变化。所有菌株都观察到了环境适应，并超过了抗性的生物成本。因此，在混合培养中，进化的抗VANA的粪肠球菌种群数量超过了其未进化的祖先敏感的粪肠球菌菌株，但仍低于进化的亲本。同样，在不选择抗生素的情况下，糖肽抗性决定因素在不选择抗生素的诺生菌小鼠的长期定植过程中也保持稳定。体内观察到VANA质粒转移。结果表明，环境适应、体内基因转移和质粒维持系统(S)有利于在不进行抗生素选择的情况下长期维持瓦那GRE，并补偿了拥有抗性基因的生物学成本。
Long-term persistence of VanA glycopeptide-resistant enterococci (GRE) has been observed in the absence of antibiotic selection. In the present study, we examined fitness parameters of a glycopeptide-susceptible Enterococcus faecium parent strain and its plasmid-mediated, VanA-resistant derivative before and after 1,000 generations in serial transfer broth cultures with or without antibiotic selection. With the exception of the vanA-containing plasmid, the strains were otherwise isogenic. The stability of the plasmid-encoded vanA resistance determinant was also investigated in vitro and in gnotobiotic mice. Competition experiments revealed that GRE with newly acquired VanA resistance had a 4% reduction in fitness relative to their susceptible parental counterpart. The relative difference in competitive fitness between resistant and susceptible strains was not significantly changed after 1,000 generations. Environmental adaptation was observed in all strains and exceeded the biological cost of resistance. Thus, the evolved VanA-resistant E. faecium populations outnumbered their unevolved ancestral susceptible E. faecium strain in mixed cultures, but remained less competitive than the evolved parent. The glycopeptide resistance determinant was similarly stably maintained during long-term colonization in gnotobiotic mice without antibiotic selection. In vivo vanA plasmid transfer was observed. The results suggest that environmental adaptation, in vivo gene transfer, and plasmid maintenance system(s) favor long-term VanA GRE persistence without antibiotic selection and compensate for the biological costs of possessing the resistance genes.