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Comparative genomic analyses of IncpA1763-KPC plasmids
Authors:Hongchao Chen  Zhe Zhan  Xiaoyuan Jiang  Yang Qing  Zhe Yin  Lingling Mei  Dongsheng Zhou  Bin Ni  Yanjun Zhang
Affiliation:1. College of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou, China;2. Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China;3. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China;4. School of Medicine, Jiangsu University, Zhenjiang, China
Abstract:Multi-replicon plasmids harboring the IncpA1763-KPC replicon together with other replicons are being increasingly reported among Enterobacteriaceae species. However, plasmids with single IncpA1763-KPC replicons are poorly studied as a different incompatibility (Inc) group, despite their rise in appearance in some strains. IncpA1763-KPC plasmids, pA1763-KPC, and p427113-2, from two clinical Klebsiella pneumoniae isolates were fully sequenced by high-throughput genome sequencing. Linear structural comparisons of IncpA1763-KPC backbone region were made between these two plasmids and six arbitrarily selected representative IncpA1763-KPC plasmids sequenced previously. A further detailed genomic comparison was carried out between plasmids pA1763-KPC, p427113-2, and pFB2.2, which show high homology across the backbone sequence to one another. Among all sequenced IncpA1763-KPC plasmids considered in this study, plasmids pA1763-KPC and p427113-2 showed the most complete IncpA1763-KPC backbones. These were composed of the IncpA1763-KPC replicon (repAIncpA1763-KPC and its iterons), the 5.6-kb IncpA1763-KPC-type maintenance region, the 27.7-kb IncFIIK-type maintenance region, and the 36.6-kb IncFIIK-type conjugal transfer regions. Compared with pA1763-KPC or p427113-2, the backbone regions of the other analyzed IncpA1763-KPC plasmids had gradually undergone different deletions or truncations, but shared small and core IncpA1763-KPC backbones including the IncpA1763-KPC replicon, IncpA1763-KPC-type maintenance region, and residual IncFIIK-type maintenance region. Accessory modules integrated into IncpA1763-KPC backbones included the multidrug-resistant module blaKPC-2 region in pA1763-KPC, the metal-resistance modules ars region together with ncr region in pFB2.2 and sil in pKPN-9a0d, the ISKpn14-to-IS26 region in p427113-2, and other non-resistance region in the respective plasmids. This detailed comparative genomics analysis of IncpA1763-KPC plasmids provides a deep insight into their diversification and evolution.
Keywords:antibiotic resistance  IncpA1763-KPC plasmids  Klebsiella pneumonia  mobile elements
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