Molecular Evolution of aKlebsiella pneumoniaeST278 Isolate Harboringbla_NDM-7and Involved in Nosocomial Transmission

Abstract

During 2013, ST278 Klebsiella pneumoniae with blaNDM-7 was isolated from the urine (KpN01) and rectum (KpN02) of a patient in Calgary, Canada. The same strain (KpN04) was subsequently isolated from another patient in the same unit. Interestingly, a carbapenem-susceptible K. pneumoniae ST278 (KpN06) was obtained 1 month later from the blood of the second patient. Next-generation sequencing (NGS) revealed that the loss of carbapenem-resistance in KpN06 was due to a 5-kb deletion on the blaNDM-7-harboring IncX3 plasmid. In addition, an IncFIB plasmid in KpN06 had a 27-kb deletion that removed genes encoding for heavy metal resistance. Phylogenetic analysis showed that the K. pneumoniae ST278 from patient 2 was likely a descendant of KpN02 and that KpN06 was a close progenitor of an environmental ST278. It is unclear whether KpN06 lost the blaNDM-7 gene in vivo. This study detailed the remarkable plasticity and speed of evolutionary changes in multidrug-resistant K. pneumoniae, demonstrating the highly recombinant nature of this species. It also highlights the ability of NGS to clarify molecular microevolutionary events within antibiotic-resistant organisms.

Plasmid-Mediated Novel bla NDM-17 Gene Encoding a Carbapenemase with Enhanced Activity in a Sequence Type 48 Escherichia coli Strain

“…KF220657) from K. pneumoniae isolated in Australia (17), and pKpN01-NDM7 (GenBank accession no. CP012990) from K. pneumoniae isolated in Canada (18). Interestingly, all six plasmids, including pNDM5_IncX3, were carried by bacteria isolated from humans, whereas the E. coli strain carrying pAD-19R in our study was isolated from a chicken.…”

Emergence of Ceftazidime-Avibactam Resistance Due to Plasmid-Borne bla KPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections

“…Therefore, patients appeared to harbor subpopulations of K. pneumoniae that evolved through different pathways from a common ancestor rather than in a direct lineage. Taken together, the findings highlight the well-recognized genetic plasticity and speed of evolutionary changes manifested by carbapenem-resistant K. pneumoniae (27).…”

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

“…Due to the highly mobile nature of bla NDM , the gene can also be lost by bacterial cells. Loss can be due to the deletion of DNA fragments as a result of insertion sequence and transposon activity, such as recombination (136,137), or the complete loss of the bla NDM -carrying plasmids (138).…”