Emerg Infect Dis. 2022 Aug;28(8):1578-1588. doi: 10.3201/eid2808.212542.
Dissemination of carbapenemase-encoding plasmids by horizontal gene transfer in multidrug-resistant bacteria is the major driver of rising carbapenem-resistance, but the conjugative mechanics and evolution of clinically relevant plasmids are not yet clear. We performed whole-genome sequencing on 1,215 clinical Enterobacterales isolates collected in Singapore during 2010-2015. We identified 1,126 carbapenemase-encoding plasmids and discovered pKPC2 is becoming the dominant plasmid in Singapore, overtaking an earlier dominant plasmid, pNDM1. pKPC2 frequently conjugates with many Enterobacterales species, including hypervirulent Klebsiella pneumoniae, and maintains stability in vitro without selection pressure and minimal adaptive sequence changes. Furthermore, capsule and decreasing taxonomic relatedness between donor and recipient pairs are greater conjugation barriers for pNDM1 than pKPC2. The low fitness costs pKPC2 exerts in Enterobacterales species indicate previously undetected carriage selection in other ecological settings. The ease of conjugation and stability of pKPC2 in hypervirulent K. pneumoniae could fuel spread into the community.
通过水平基因转移在多药耐药细菌中传播的碳青霉烯酶编码质粒是导致碳青霉烯类耐药性上升的主要因素，但临床上相关质粒的接合机制和进化尚不清楚。我们对 2010 年至 2015 年期间在新加坡收集的 1215 株临床肠杆菌科分离株进行了全基因组测序。我们鉴定了 1126 个碳青霉烯酶编码质粒，并发现 pKPC2 正在成为新加坡的主要质粒，取代了早期的主导质粒 pNDM1。pKPC2 经常与许多肠杆菌科物种（包括高毒力肺炎克雷伯菌）发生共轭，并且在没有选择压力和最小适应性序列变化的情况下在体外保持稳定性。此外，与供体和受体对之间的分类相关性降低相比，荚膜是 pNDM1 比 pKPC2 更大的共轭障碍。pKPC2 在肠杆菌科物种中施加的低适应性成本表明，在其他生态环境中存在以前未检测到的携带选择。pKPC2 在高毒力肺炎克雷伯菌中的易共轭性和稳定性可能会助长其在社区中的传播。
