The iucC gene is a major contributor to the virulence of hypervirulent Klebsiella pneumoniae

iucC基因是高毒力肺炎克雷伯菌毒力的主要贡献者。

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Abstract

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKp) is a critical pathogen that causes highly lethal invasive infections with its virulence linked to that of aerobactin, the core siderophore system of hvKp. METHODS: Here, 20 porcine-derived K. pneumoniae strains were subjected to capsular genotyping and the virulence of the strains was evaluated through mouse lethality assays. Whole-genome sequencing and analysis was performed on two K2 serotype strains (including highly and weakly virulent strains), and the differential virulence genes were analyzed. The virulence-related gene iucC, identified in the hypervirulent K2 serotype strain KP10, was knocked out using homologous recombination to preliminarily explore its function in K. pneumoniae. RESULTS: In this study, a highly virulent K2-type strain KP10 and a low virulent K2-type strain KP6 were screened from 20 strains of porcine K. pneumoniae. The results of the genome and virulence gene analyses revealed that compared with KP6, the highly virulent strain KP10 specifically encodes the iucC gene. The △ iucC mutant of the high-virulence strain KP10 exhibited significantly reduced biofilm formation, decreased siderophore production, moderate serum sensitivity, and attenuated virulence. Furthermore, the mutant displayed decreased adhesion to IPEC-J2 cells, reduced cytotoxicity, and decreased cell mortality. These results revealed that iucC is a major contributor to virulence in the KP10 hvKp strain. Notably, iucC genes were detected in the genomes of K. pneumoniae from humans and six different animal and environmental sources, and some iucC genes were shared in K. pneumoniae from these sources. CONCLUSION: Overall, this work provides a crucial theoretical foundation for elucidating iucC function and the pathogenesis of K. pneumoniae. Its widespread presence in different hosts and environments considerably increases the risk of cross species transmission and public health events.

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