Wang Jiayun, Ji Xing, García Pilar, Li Jun, Zhang Lili, Wang Heng, Wang Ran, He Tao
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing 210040, China.
Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing 210040, China.
Microbiol Res. 2025 Oct;299:128242. doi: 10.1016/j.micres.2025.128242. Epub 2025 May 27.
The global emergence of hypervirulent Klebsiella pneumoniae (hvKP) poses significant threats to public health. The iucABCD (iuc) operon, a plasmid-borne genetic determinant encoding the siderophore aerobactin, serves as a reliable biomarker for hvKP identification. This study aimed to characterize the iuc3 (type 3 iuc)-positive K.pneumoniae isolates from diseased cows as hvKP strains and to elucidate the contribution of iuc3-positive plasmids to the hypervirulence phenotype, the evolutionary pathways and the spreading risk of the iuc3-positive plasmids. Eight of 108 K. pneumoniae isolates from 763 cow milk samples contained the iuc3 operon, and all iuc3 operons were located on T4SS-bearing plasmids. Notably, these isolates showed hypervirulent phenotype compared to the iuc3 knockout and plasmid-cured strains, including severe tissue damage, high bacterial loads in typical organs and high mortality in animal models. Analysis of NCBI database showed iuc3-positive K. pneumoniae strains have been widely distributed across animal, food, and humans, and exhibit an independent evolutionary pathways compared to the human-associated iuc1-type hvKP. The IS elements likely drive the acquisition of various resistance genes and the emergence of iuc3-positive resistance plasmids. The iuc3-bearing plasmids in this study demonstrated highly conjugative ability, low fitness costs, and the ability to replace the iuc1-bearing classical virulence plasmid in human hvKP strain. Besides, they could completely fuse with broad-host-range resistance plasmid (IncX3-bla), becoming carbapenem-resistant hvKP strains. The iuc3- and bla- fusion plasmids showed strong in vivo retention and dissemination capabilities in mouse models. Our findings emphasize the necessity for long-term monitoring of iuc3-positive plasmids in K. pneumoniae isolates from both animals and humans.
高毒力肺炎克雷伯菌（hvKP）在全球范围内的出现对公众健康构成了重大威胁。iucABCD（iuc）操纵子是一种编码铁载体气杆菌素的质粒携带的遗传决定因素，是鉴定hvKP的可靠生物标志物。本研究旨在将来自患病奶牛的iuc3（3型iuc）阳性肺炎克雷伯菌分离株鉴定为hvKP菌株，并阐明iuc3阳性质粒对高毒力表型、进化途径以及iuc3阳性质粒传播风险的贡献。从763份牛奶样本中分离出的108株肺炎克雷伯菌中有8株含有iuc3操纵子，所有iuc3操纵子都位于携带IV型分泌系统（T4SS）的质粒上。值得注意的是，与iuc3基因敲除和质粒消除菌株相比，这些分离株表现出高毒力表型，包括严重的组织损伤、典型器官中的高细菌载量以及动物模型中的高死亡率。对NCBI数据库的分析表明，iuc3阳性肺炎克雷伯菌菌株已广泛分布于动物、食品和人类中，并且与人类相关的iuc1型hvKP相比呈现出独立的进化途径。插入序列（IS）元件可能推动了各种耐药基因的获得以及iuc3阳性耐药质粒的出现。本研究中的携带iuc3的质粒表现出高度的接合能力、低适应性代价，以及在人源hvKP菌株中取代携带iuc1的经典毒力质粒的能力。此外，它们可以与广泛宿主范围的耐药质粒（IncX3-bla）完全融合，成为耐碳青霉烯类的hvKP菌株。iuc3和bla融合质粒在小鼠模型中表现出强大的体内保留和传播能力。我们的研究结果强调了对动物和人类肺炎克雷伯菌分离株中iuc3阳性质粒进行长期监测的必要性。
