Anti-restriction protein ArdA promotes clinical Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae spread and its molecular mechanism. (28th December 2022)

• Record Type: Journal Article
• Authors: Chen, Huimin; Tao, Shuan; Li, Na; Zhu, Qing; Liu, Liping; Fang, Yeiwei; Xu, Yao; Liang, Wei
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 78:Number 2(2023)
• Page Start: 521
• Page End: 530
• Publication Date: 2022-12-28
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkac423
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has spread worldwide and has become a major threat to public health. The restriction modification system provides an innate defence of bacteria against plasmids or transposons, while many different types of plasmid encoding the anti-restriction protein ArdA can specifically affect the restriction activity in bacteria. Objectives: To detect the codistribution of ArdA and bla KPC-2 plasmids in KPC-KP and explore the molecular mechanism of ArdA promoting KPC-KP spread. Methods: We collected 65 clinical CRKP isolates from Ningbo, China, and 68 cases of plasmid complete sequences in GenBank to determine the prevalence of ArdA gene on the K. pneumoniae bla KPC-2 plasmid. The anti-restriction function of ArdA in promoting horizontal gene transfer (HGT) was verified by transformation, conjugation and transduction methods, and the pull-down experiment was used to investigate the molecular mechanism of ArdA protein in vitro . Results: We found that ArdA was widely distributed in KPC-KP in 100% of cases, which was detected in 0% of drug susceptible K. pneumoniae, and the plasmids containing the ArdA gene in 90% of the 30 cases randomly retrieved from the database. We also verified that ArdA has a good anti-restriction function ( P < 0.05) through two aspects of HGT (transformation, transduction), and explored the non-occurrence interaction of ArdA and the hsdM subunit protein of EcoKI enzyme from the perspective of protein molecules. Conclusions: These findings suggest that the coexistence advantage of ArdA with the bla KPC-2 plasmids may provide KPC-producing K. pneumoniae with a very efficient evasion of the restriction of type I systems, which not only favours ArdA-containing mobile genetic elements in the same species HGT between bacteria also facilitates HGT between other bacterial species.