Abstract
The emergence of carbapenem-resistant Proteus represents a serious threat to global public health due to limited antibiotic treatment options. Here, we characterize a Proteus isolate NMG38-2 of swine origin that exhibits extensive drug resistance, including carbapenems. Whole-genome sequencing based on Illumina and MinION platforms showed that NMG38-2 contains 24 acquired antibiotic resistance genes and three plasmids, among which, pNDM_NMG38-2, a pPvSC3-like plasmid, is transferable and co-carries blaNDM-1 and lnu(G). Sequence analysis of pPvSC3-like plasmids showed that they share a conserved backbone but have a diverse accessory module with complex chimera structures bearing abundant resistance genes, which are facilitated by transposons and/or homologous recombination. The acquisition of blaNDM-1 in pNDM_NMG38-2 was due to the ISCR1-mediated integration event. Comprehensive analysis of the lnu(G)-bearing cassettes carried by bacterial plasmids or chromosomes revealed a diversification of its genetic contexts, with Tn6260 and ISPst2 elements being the leading contributors to the dissemination of lnu(G) in Enterococcus and Enterobacteriaceae, respectively. In conclusion, this study provides a better understanding of the genetic features of pPvSC3-like plasmids, which represent a novel plasmid group as a vehicle mediating the dissemination of blaNDM-1 among bacteria species. Moreover, our results highlight the central roles of Tn6260 and ISPst2 in the spread of lnu(G).
Highlights
Proteus is a member of Enterobacteriaceae and ranks third in regard to the cause of hospital-acquired infections [1]
The blaNDM gene is largely carried on plasmids with a variety of replicon types [3], which play a vital role in the wide dissemination of blaNDM
The species identification was performed by genome-to-genome sequence comparison of NMG38-2 and the reference strains of known Proteus species
Summary
Proteus is a member of Enterobacteriaceae and ranks third in regard to the cause of hospital-acquired infections [1]. Proteus species are intrinsically resistant to polymyxin, tigecycline, and nitrofurantoin [2], and the acquisition of additional carbapenem resistance is of particular concern. Strains producing the New Delhi metallo-β-lactamase (NDM), which is able to hydrolyze almost all of the β-lactams (including carbapenems), except monobactam, severely limit therapeutic options for treating infections caused by them [3]. The blaNDM gene, since its initial identification in India in 2009 [4], has spread worldwide. The blaNDM gene is largely carried on plasmids with a variety of replicon types [3], which play a vital role in the wide dissemination of blaNDM.
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