Comparative genomic analyses of IncpA1763-KPC plasmids

Abstract

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.

Keywords: IncpA1763-KPC plasmids; Klebsiella pneumonia; antibiotic resistance; mobile elements.