Xu Qi, Sun Ruanyang, Liu Xiaoxuan, Heng Heng, Yang Xuemei, Xie Miaomiao, Yang Chen, Ye Lianwei, Chan Edward Wai-Chi, Zhang Rong, Chen Sheng
State Key Laboratory of Chemical Biology and Drug Discovery and the Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China.
Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China.
mSystems. 2025 Apr 22;10(4):e0167524. doi: 10.1128/msystems.01675-24. Epub 2025 Mar 25.
Carbapenem-resistant hypervirulent (CR-hv) has led to a high mortality rate in the clinical setting and garnered significant attention in the clinical and scientific communities. It is still not clear which major mechanisms mediate the rapid evolution of hv in clinical settings since the plasmid-encoding hypervirulence phenotype is considered non-conjugative. In this study, we revealed a conjugative plasmid, p16HN200-Vir, encoding virulence-associated operon () and resulting in a hypervirulent phenotype. analysis of strains from NCBI predicted a total of 94 p16HN200-Vir-like conjugative virulence plasmids. These sequences were identified in 19 sequence types (STs) of the host with significant geographical variations in distribution across countries and continents. Notably, ST11 was predominant in China, while ST147 and ST395 were prominent in the United Kingdom and Russia, respectively. These plasmids could be categorized into seven lineages, some of which formed distinct geographical clusters in China and the UK, while others exhibited a hybrid population. Importantly, most of the plasmids carried different carbapenemases, including a (lineage 6 and 7), and (lineage 2 and 5). Specifically, plasmids recovered from the United Kingdom and Russia were lineage-specific, with present in lineage 6 and in lineage 7. Our data suggest that this type of conjugative plasmids has spread around the world and contributed significantly to the current rapid evolution of CR-hv in clinical settings. Further surveillance of these types of conjugative plasmids in clinical is warranted.
In this study, we found that the conjugative virulence plasmids containing carbapenem resistance genes could be conjugated to strains, enabling them to express antibiotic resistance and hypervirulence-associated phenotypes simultaneously. More importantly, we observed that the global dissemination of this type of multidrug resistance and hypervirulence conjugative plasmid is lineage specific. The UMAP projection revealed that the regional variations were correlated with ST types and serotypes, which poses a global threat of the CR-hv infection worldwide.
耐碳青霉烯高毒力（CR-hv）在临床环境中导致了高死亡率，并在临床和科学界引起了广泛关注。由于编码高毒力表型的质粒被认为是非接合性的，目前尚不清楚哪些主要机制介导了高毒力在临床环境中的快速进化。在本研究中，我们发现了一种接合质粒p16HN200-Vir，它编码与毒力相关的操纵子，并导致高毒力表型。对来自NCBI的菌株分析预测共有94种p16HN200-Vir样接合毒力质粒。这些序列在宿主的19种序列类型（STs）中被鉴定出来，在不同国家和大陆的分布存在显著的地理差异。值得注意的是，ST11在中国占主导地位，而ST147和ST395分别在英国和俄罗斯较为突出。这些质粒可分为七个谱系，其中一些在中国和英国形成了不同的地理集群，而另一些则呈现出混合群体。重要的是，大多数质粒携带不同的碳青霉烯酶，包括A类（谱系6和7）和D类（谱系2和5）。具体而言，从英国和俄罗斯分离出的质粒具有谱系特异性，A类存在于谱系6中，D类存在于谱系7中。我们的数据表明，这种类型的接合质粒已在全球传播，并对目前临床环境中CR-hv的快速进化做出了重大贡献。有必要对临床环境中的这类接合质粒进行进一步监测。
在本研究中，我们发现含有碳青霉烯耐药基因的接合毒力质粒可以与肺炎克雷伯菌菌株接合，使它们能够同时表达抗生素耐药性和高毒力相关表型。更重要的是，我们观察到这种类型的多药耐药和高毒力接合质粒的全球传播具有谱系特异性。UMAP投影显示区域差异与ST类型和血清型相关，这对全球范围内的CR-hv感染构成了全球威胁。
