Emergence of Hybrid Resistance and Virulence Plasmids Harboring New Delhi Metallo-β-Lactamase in Klebsiella pneumoniae in Russia

Abstract

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a new threat to healthcare. In this study, we analyzed nine CR-hvKp isolates of different sequence-types (ST) recovered from patients with nosocomial infections in two hospitals in Saint Petersburg. Whole-genome sequencing showed that eight of them harbored large mosaic plasmids carrying resistance to carbapenems and hypervirulence simultaneously, and four different types of hybrid plasmids were identified. BLAST analysis showed a high identity with two hybrid plasmids originating in the UK and Czech Republic. We demonstrated that hybrid plasmids emerged due to the acquisition of resistance genes by virulent plasmids. Moreover, one of the hybrid plasmids carried a novel New Delhi metallo-beta-lactamase (NDM) variant, differing from NDM-1 by one amino acid substitution (D130N), which did not provide significant evolutionary advantages compared to NDM-1. The discovery of structurally similar plasmids in geographically distant regions suggests that the actual distribution of hybrid plasmids carrying virulence and resistance genes is much wider than expected.

Corrigendum: Genetic and Phenotypic Characterization of the Novel Metallo-β-Lactamase NDM-29 From Escherichia coli

“…“Currently, the mutation of D130G has been reported in NDM- 14, and kinetic analysis indicated that NDM-14 has greater carbapenem resistance with a higher affinity for imipenem and meropenem (Zou et al, 2015). Based on our research, there is no difference between NDM-1 and NDM-29 in terms of susceptibility to carbapenems, which is in accordance with the findings of Starkova et al ( 2021 ).”…”

“…Microbiol. 12:743981. doi: 10.3389/fmicb.2021.743981 In the original article, Starkova et al (2021) was not cited in the article. The citation has now been inserted in Introduction, paragraph 2 and Discussion, paragraph 3.…”

“…“In a recent study, we discovered an NDM-29 carbapenemase- producing E. coli strain (19NC225), isolated from a patient's bile in 2019. The gene sequence of bla NDM−29 from a Klebsiella pneumoniae strain has been submitted to the NCBI database (NCBI), by researchers from Saint Petersburg, Russia (Starkova et al, 2021 ). Our study is the first detailed report of NDM-29 from E. coli in China, including genetic and phenotypic characterization, and confirms the potential threat of this new NDM-type carbapenemase to be a cause of extensively drug-resistant organism spread.”…”

Anatomy of an extensively drug-resistant Klebsiella pneumoniae outbreak in Tuscany, Italy

“…As expected, susceptibility to the aminoglycosides and/or carbapenems was restored in these isolates ( Dataset S2 ). Finally, while the backbone of pSI0739-NDM was lost (event L) in isolate 752019, bla NDM-1 , carried on a Tn 125 -like transposon ( 21 , 22 ), integrated into the canonical pSI0739-ARMA-Vir plasmid, resulting in the de novo formation of hybrid plasmid pSI0646A-ARMA-Vir-NDM. Importantly, near-identical hybrid plasmids carrying determinants for virulence, carbapenem ( bla NDM ), and broad-spectrum aminoglycoside resistances are now emerging in isolates from various countries in both ST-147 and distinct convergent K. pneumoniae lineages ( SI Appendix , Fig.…”

“…Importantly, near-identical hybrid plasmids carrying determinants for virulence, carbapenem ( bla NDM ), and broad-spectrum aminoglycoside resistances are now emerging in isolates from various countries in both ST-147 and distinct convergent K. pneumoniae lineages ( SI Appendix , Fig. S3 ) ( 6 , 14 , 16 , 22 ).…”