Comparative genomic analysis of Klebsiella reveals extensive transmission of resistance genes mediated by multireplicon resistance plasmids

Abstract:

[Objective] To study the relationship between Klebsiella and multireplicon resistance plasmids, and to analyze the mechanism of multireplicon plasmid carrier in response to antibiotic pressure.[Methods] We collected fifty-six isolates of Klebsiella from different wild animals and environments during 2018 to 2020. We analyzed the multidrug resistance (MDR) phenotype by microbroth dilution method, sequenced and analyzed the representative isolates by bacterial genome-wide association study (BGWAS).[Results] Our results revealed that the isolates from non-human sources showed a more extensive drug resistance, and especially stronger resistance to ampicillin (reach 80.36%). In particular, the isolates from Malay pangolin were highly resistant to cephalosporins, chloramphenicol, levofloxacin and sulfamethoxazole. Genomic analysis showed that the resistance plasmids carried by these isolates were related to carry many antibiotic resistance genes. Further analysis of 69 plasmids demonstrated that 28 plasmids were multireplicon plasmids, mainly carrying beta-lactamase genes such as bla_CTX-M-15, bla_CTX-M-14, bla_CTX-M-55, bla_OXA-1 and bla_TEM-1. According to the analysis of plasmids carried by different isolates, Klebsiella pneumoniae may be an important host of multireplicon plasmid. Plasmid skeleton and structure analysis showed that multireplicon plasmid was formed by the fusion of two or more single plasmids, which made the isolates strong adaptability to the antibiotic environment, and increased the ability of drug-resistant isolates to spread around the world year by year.[Conclusion] The phenotype of multidrug-resistant bacteria is related to the carrying multireplicon plasmid.Multireplicon plasmid has a stronger ability to carry resistance genes than non-multireplicon plasmid, which may be an important mechanism for bacteria response to adapt to stronger antibiotic pressure environment. This phenomenon is of great significance for exploring the transmission and diffusion mechanism of bacterial resistance genes in the future.