Genomic features and fitness cost of co-existence of bla (KPC-2) and bla (VIM-2) plasmids in ICU-derived pan-drug resistant Pseudomonas aeruginosa

ICU来源的泛耐药铜绿假单胞菌中bla(KPC-2)和bla(VIM-2)质粒共存的基因组特征和适应性代价

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Abstract

BACKGROUD: The emergence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) co-producing KPC-2 and VIM-2 has increased the healthcare threats. RESULTS: In this study, a CRPA strain 18102011, was isolated from the bile of a burn patient in ICU of China. Its whole genome was sequenced via the PacBio platform. The molecular characteristics of the genome were analyzed to assess the genetic environment of the carbapenemase genes bla (KPC-2) and bla (VIM-2). Antimicrobial susceptibility, plasmid stability, bacterial growth curves, and plasmid conjugation were measured. Strain 18102011 exhibited a resistant pattern to all 23 antibiotics tested, which could be defined as a pan-drug resistant P. aeruginosa strain. Two plasmids were identified in this strain: the Inc(pRBL16) mega-plasmid pP2011-1 carrying bla (VIM-2) and the IncP6 plasmid pP2011-2 carrying bla (KPC-2). bla (VIM-2) was located in the region of In2057 (a novel class 1 integron) that was inserted into pP2011-1, and the expression of the bla (VIM-2) gene was increased by the PcW(TGN-10) promoter located at the 5'-CS. For the bla (KPC-2) gene, the core module Tn3-ISKpn27-bla (KPC)-ΔISKpn6 served as the bla (KPC-2) platform in pP2011-2, and the expression of the bla (KPC-2) gene was achieved via the P1 promoter located downstream of ISKpn27. This expression pattern resulted in MICs of 4,096 μg/mL of imipenem for both strain 18102011 and its transconjugant D2011. Both plasmids were stable in strain 18102011 and could be co-transferred to other strains. CONCLUSION: This study raised concerns regarding the high stability and non-inferior fitness of bla (KPC-2)-bla (VIM-2)-CRPA, shed light on its genomic characteristics, and underscored the importance of continued surveillance of CRPA.

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