Abstract

Co-occurrence of hypervirulence and KPC-2 carbapenem resistant phenotypes in a highly-transmissible ST11 clone ofKlebsiella pneumoniae has elicited deep concerns from public health stand point. To address this puzzle, we conducted a large-scale epidemiological, clinical and genomic study of K. pneumonia ST11 clones with both hypervirulence and carbapenem resistance in two tertiary hospitals in Zhejiang province. Most of the patients (15/23) were diagnosed with exclusively carbapenem-resistant K. pneumoniae (CRKP) infections. Ten death cases were reported, some of which are due to the failure of antibiotic therapies. As a result, we identified one new rare sequence types (ST449) to KPC-2-producing CRKP, in addition to the dominant ST11. These clinical isolates of K. pneumoniae are multi-drug resistant and possess a number of virulence factors. Experimental infections of wax moth larvae revealed the presence of hypervirulence at varied level, suggesting the complexity in bacterial virulence factors. However, plasmid curing assays further suggested that the rmpA2-virulence plasmid is associated with, but not sufficient for neither phenotypic hypermucoviscosity nor virulence of K. pneumoniae. Intriguingly, all the rmpA2 genes were found to be inactive due to genetic deletion. In total, we reported 21 complete plasmid sequences comprising 13 rmpA2-positive virulence plasmids and 8 bla _KPC-2-harboring resistance plasmids. In addition to the prevalent pLVKP-like virulence plasmid variants (~178kb), we found an unexpected diversity among KPC-2-producing plasmids whose dominant form is IncFII-IncR type (~120kb), rather than the previously anticipated version of ~170kb. These findings provide an updated snapshot of convergence of hypervirulence and carbapenem resistance in ST11 K. pneumoniae.

摘要

高毒力和 KPC-2 碳青霉烯类耐药表型在肺炎克雷伯菌的高传染性 ST11 克隆中同时出现， 这引起了公共卫生方面的深切关注。为了解决这个难题，我们 在浙江省的两家三级医院对具有高毒力和碳青霉烯类耐药性的肺炎克雷伯菌ST11 克隆进行了大规模的流行病学、临床和基因组研究 。大多数患者 (15/23) 被诊断为完全耐碳青霉烯 K。 肺炎链球菌 (CRKP) 感染。报告了 10 例死亡病例，其中一些是由于抗生素治疗失败造成的。因此，除了占主导地位的 ST11 之外，我们还为产生 KPC-2 的 CRKP 鉴定了一种新的稀有序列类型 (ST449)。这些肺炎克雷伯菌的临床分离株  具有多重耐药性并具有多种毒力因子。蜡蛾幼虫的实验感染揭示了不同水平的超毒力的存在，表明细菌毒力因子的复杂性。然而，质粒治愈试验进一步表明 rmpA2毒力质粒与K 的表型高粘滞性和毒力相关，但不充分 。 肺炎。有趣的是，所有的 rmpA2 发现基因由于基因缺失而失活。我们总共报告了 21 个完整的质粒序列，包括 13 个 rmpA2阳性毒力质粒和 8 个 bla _KPC-2携带抗性质粒。除了流行的 pLVKP 样毒力质粒变体（~178kb）之外，我们还发现了主要形式是 IncFII-IncR 型（~120kb）的 KPC-2 生产质粒之间的意外多样性，而不是之前预期的~170kb 版本. 这些发现提供了 ST11肺炎克雷伯菌中超毒力和碳青霉烯耐药性收敛的最新快照 。