Comparative Genomic Analyses Of Inc(Pa1763-Kpc) Plasmids

Multi-replicon plasmids harboring the Inc(pA1763-KPC) replicon together with other replicons are being increasingly reported among Enterobacteriaceae species. However, plasmids with single Inc(pA1763-KPC) replicons are poorly studied as a different incompatibility (Inc) group, despite their rise in appearance in some strains. Inc(pA1763-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 Inc(pA1763-KPC) backbone region were made between these two plasmids and six arbitrarily selected representative Inc(pA1763-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 Inc(pA1763-KPC) plasmids considered in this study, plasmids pA1763-KPC and p427113-2 showed the most complete Inc(pA1763-KPC) backbones. These were composed of the Inc(pA1763-KPC) replicon (repA(IncpA1763-KPC) and its iterons), the 5.6-kb Inc(pA1763-KPC)-type maintenance region, the 27.7-kb IncFII(K)-type maintenance region, and the 36.6-kb IncFII(K)-type conjugal transfer regions. Compared with pA1763-KPC or p427113-2, the backbone regions of the other analyzed Inc(pA1763-KPC) plasmids had gradually undergone different deletions or truncations, but shared small and core Inc(pA1763-KPC) backbones including the Inc(pA1763-KPC) replicon, Inc(pA1763-KPC)-type maintenance region, and residual IncFII(K)-type maintenance region. Accessory modules integrated into Inc(pA1763-KPC) backbones included the multidrug-resistant module bla(KPC-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 Inc(pA1763-KPC) plasmids provides a deep insight into their diversification and evolution.