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.
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; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
Microbiol Res. 2024 Dec;289:127896. doi: 10.1016/j.micres.2024.127896. Epub 2024 Sep 5.
Klebsiella pneumoniae (Kp) is increasingly recognized as a reservoir for a range of antibiotic resistance genes and a pathogen that frequently causes severe infections in both hospital and community settings. In this study, we have identified a novel mechanism of conjugative transfer of a non-conjugative virulence plasmid through the formation of a fusion plasmid between the virulence plasmid and a novel 59,162 bp IncN- plasmid. This plasmid was found to be a multidrug-resistance (MDR) plasmid and carried a T4SS cluster, which greatly facilitated the efficient horizontal transfer of the fusion plasmid between Kp strains. The fused virulence plasmid conferred the resistance of serum killing and macrophage phagocytosis to the transconjugants. Importantly, this plasmid was shown to be essential for Kp virulence in a mouse model. Mechanistic analysis revealed that the virulence factors encoded by this virulence plasmid contributed to resistance to in vivo clearance and induced a high level of proinflammatory cytokine IL-1β, which acts as an inducer for more neutrophil recruitment. The transmission of the fusion plasmid in Kp has the potential to convert it into both MDR and hypervirulent Kp, accelerating its evolution, and posing a serious threat to human health. The findings of this study provide new insights into the rapid evolution of MDR and hypervirulent Kp in recent years.
肺炎克雷伯菌（Kp）越来越被认为是一系列抗生素耐药基因的储库，也是一种经常在医院和社区环境中引起严重感染的病原体。在本研究中，我们发现了一种新的非接合性毒力质粒通过毒力质粒与新型 59,162 bp IncN-质粒之间形成融合质粒进行接合转移的机制。该质粒被鉴定为多药耐药（MDR）质粒，并携带一个 T4SS 簇，这极大地促进了融合质粒在肺炎克雷伯菌菌株之间的有效水平转移。融合后的毒力质粒赋予了转导体对血清杀伤和巨噬细胞吞噬的抗性。重要的是，该质粒被证明是肺炎克雷伯菌在小鼠模型中致病所必需的。机制分析表明，该毒力质粒编码的毒力因子有助于抵抗体内清除，并诱导高水平的促炎细胞因子 IL-1β，后者作为更多中性粒细胞募集的诱导剂。融合质粒在肺炎克雷伯菌中的传播有可能使其转化为多药耐药和超毒力肺炎克雷伯菌，加速其进化，并对人类健康构成严重威胁。本研究的发现为近年来多药耐药和超毒力肺炎克雷伯菌的快速进化提供了新的见解。
