Genomic Epidemiology of NDM-1-Encoding Plasmids in Latin American Clinical Isolates Reveals Insights into the Evolution of Multidrug Resistance

Abstract

Bacteria that produce the broad-spectrum Carbapenem antibiotic New Delhi Metallo-β-lactamase (NDM) place a burden on health care systems worldwide, due to the limited treatment options for infections caused by them and the rapid global spread of this antibiotic resistance mechanism. Although it is believed that the associated resistance gene blaNDM-1 originated in Acinetobacter spp., the role of Enterobacteriaceae in its dissemination remains unclear. In this study, we used whole genome sequencing to investigate the dissemination dynamics of blaNDM-1-positive plasmids in a set of 21 clinical NDM-1-positive isolates from Colombia and Mexico (Providencia rettgeri, Klebsiella pneumoniae, and Acinetobacter baumannii) as well as six representative NDM-1-positive Escherichia coli transconjugants. Additionally, the plasmids from three representative P. rettgeri isolates were sequenced by PacBio sequencing and finished. Our results demonstrate the presence of previously reported plasmids from K. pneumoniae and A. baumannii in different genetic backgrounds and geographically distant locations in Colombia. Three new previously unclassified plasmids were also identified in P. rettgeri from Colombia and Mexico, plus an interesting genetic link between NDM-1-positive P. rettgeri from distant geographic locations (Canada, Mexico, Colombia, and Israel) without any reported epidemiological links was discovered. Finally, we detected a relationship between plasmids present in P. rettgeri and plasmids from A. baumannii and K. pneumoniae. Overall, our findings suggest a Russian doll model for the dissemination of blaNDM-1 in Latin America, with P. rettgeri playing a central role in this process, and reveal new insights into the evolution and dissemination of plasmids carrying such antibiotic resistance genes.

Genomic analysis of a multidrug‐resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon

“…Although the contig bearing the A/C 2 replicase gene did not harbor the class 1 integrase and associated gene cassettes, we would not be surprised if further genomic sequencing proves this to be the case. Notably, A/C plasmids have not been reported in P. rettgeri as far as we are aware, although it has been previously described in P. stuartii in Tunisia, Mexico, and other countries . Particularly, the ability of this plasmid group to mobilize many ARGs and transfer them between different bacterial species, including commensals and pathogens, and from animals to humans makes this finding worrying .…”

“…Notably, A/C plasmids have not been reported in P. rettgeri as far as we are aware, although it has been previously described in P. stuartii in Tunisia, Mexico, and other countries. 1,38 Particularly, the ability of this plasmid group to mobilize many ARGs and transfer them between different bacterial species, including commensals and pathogens, and from animals to humans makes this finding worrying. 39 We thus suggest that further studies be undertaken in South Africa to trace the epidemiology of this plasmid and its association with ARGs.…”

“…Providencia rettgeri is a Gram‐negative opportunistic human pathogenic bacterium that belongs to Proteae bacteria, which comprises the Morganella and Proteus genera. It is found in hospital settings and is mainly associated with urinary tract infections (UTI) . P. rettgeri has also been reported to cause other infections, such as bacteremia, eye infections, meningitis, endocarditis, pneumonia, UTI, and diarrhea .…”

“…It is found in hospital settings and is mainly associated with urinary tract infections (UTI). 1 P. rettgeri has also been reported to cause other infections, such as bacteremia, eye infections, meningitis, endocarditis, pneumonia, UTI, and diarrhea. 2,3 P. rettgeri is intrinsically resistant to colistin and tigecycline, 4 which can be transferred horizontally to Escherichia coli, and generally resistant to gentamycin, tobramycin, aminopenicillins, and first-generation cephalosporins.…”

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

“…Although bla NDMcarrying IncX3 plasmids have been found in Europe and North America, most of the plasmids deposited in GenBank (80/117; 68.4%) have been recovered in China and neighboring countries, such as South Korea (n ϭ 7), Vietnam (n ϭ 2), and Myanmar cgST1.2 of IncC warrant further investigation to understand their epidemiology, their true contribution to the NDM problem, and the mechanisms mediating their wide spread. Plasmids carrying bla NDM have been well documented in Acinetobacter (e.g., see references [107][108][109][110]. A replicon typing scheme for plasmids of A. baumannii has been developed (111), but the replicon types of bla NDM -carrying plasmids in Acinetobacter have rarely been reported, and the scheme has not been incorporated into Plasmid-Finder or any other commonly used plasmid typing tools.…”