Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying bla_IMP by whole-genome sequencing and Southern blotting. bla_IMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of bla_IMP-6 caused an outbreak likely through covert transmission of bla_IMP-6. For stable carriage of bla_IMP-6, they occasionally integrated bla_IMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in bla_IMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments.

中文翻译：

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编码碳青霉烯酶的质粒的表征和耐碳青霉烯的肠杆菌科细菌传播的机制

由于有限的治疗选择，发病率和死亡率高的耐碳青霉烯肠杆菌（CRE）感染构成严重的临床挑战。先前对来自日本大阪43家医院的1,507名患者进行的CRE监测研究表明，有12％的患者携带CRE，而95％的CRE分离株是IMP型碳青霉烯酶生产商。在这里，研究了单个碳青霉烯酶基因的这种区域传播的机制。由于CRE的传播主要归因于质粒上碳青霉烯酶基因的传播，因此我们通过全基因组测序和Southern印迹分析了230个带有bla _IMP的CRE分离株的质粒组。bla _IMP-6发现p53PI主要通过pKPI-6质粒在染色体不同的分离株中传播。在pKPI-6广泛传播的基础上，鉴定了衍生自pKPI-6的各种亚群，这些亚群在CRE分离物的传播方面具有优势。通过bla _IMP-6的转录调控表现出对美洛培南的异抗性的簇可能通过bla _IMP-6的隐性传播引起了暴发。为了稳定携带bla _IMP-6，他们有时在其染色体上整合了bla _IMP-6。此外，我们检测到了一种分离物，该分离物通过单点突变扩大了抗菌素耐药性的范围。pKPI-6上的bla _IMP -6。对质粒组的多方面分析使我们对CRE分离物的水平扩散有了更准确的认识，这仅通过比较整个基因组就很难追踪。这项研究揭示了特定的碳青霉烯酶编码质粒的广泛传播，伴随着表型多样的衍生物的出现，这可能促进CRE在各种环境中的进一步传播。