Occurrence of NDM-1-producing Morganella morganii and Proteus mirabilis in a single patient in Portugal: probable in vivo transfer by conjugation

Abstract

Objectives To decipher the genetics of acquisition of carbapenemase-encoding genes identified in two carbapenem-resistant Enterobacteriaceae recovered from a single patient in Portugal. Methods Carbapenemase genes were searched by PCR assays and mating-out assays were performed to further characterize the plasmid support of the carbapenemase genes. Genetic characterization of the plasmid supports was performed by whole-plasmid sequencing using the Illumina technology. Results We identified here two NDM-1-producing isolates, namely a Morganella morganii and a Proteus mirabilis, sharing the same blaNDM-1-positive plasmid. This 154 kb plasmid belonged to the IncA/C2 type, recently renamed IncC, and co-harboured two AmpC β-lactamase genes, namely blaCMY-4 and blaDHA-1, in addition to the 16S rRNA methylase gene armA encoding high-level resistance to aminoglycosides. In addition, the M. morganii isolate produced the CTX-M-33 extended-spectrum β-lactamase possessing weak carbapenemase activity, encoded by another plasmid. Conclusions We showed here that, in addition to KPC-type and OXA-181 carbapenemases, which have been identified as widespread in this country, another concern is the emergence of NDM-1-producing enterobacterial isolates in Portugal. We demonstrated here the in vivo plasmid transfer of a blaNDM-1-positive plasmid leading to dissemination of this carbapenemase gene within different enterobacterial species in a single patient.

High Colonization Rate and Heterogeneity of ESBL- and Carbapenemase-Producing Enterobacteriaceae Isolated from Gull Feces in Lisbon, Portugal

“…GES-5 and GES-6 have been found sporadically, with the exception of one hospital in Lisbon where K. pneumoniae isolates co-harboring bla KPC-3 and bla GES-5 represented 17% of the isolates [ 16 ]. Although NDM producers have been recently detected in a single patient in Lisbon [ 18 ], no bla NDM-1 was found in gulls in our study, suggesting its still low diffusion rate. While ST940 was the predominant E. coli background identified from gulls in our study, this ST had not been identified in Portugal before and, to the best of our knowledge, has been exclusively identified among NDM-5-producing E. coli isolates in the US [ 36 ].…”

“…GES-5 was mainly found sporadically with the exception of one hospital in Lisbon, where it represented 17% of the carbapenemase-producing K. pneumoniae isolates [ 16 ]. Although NDM producers have been recently detected in a single patient in Lisbon [ 18 ], they are still infrequent in the country.…”

Cross-Border Emergence of Escherichia coli Producing the Carbapenemase NDM-5 in Switzerland and Germany

“…Plasmid transfer studies. The transferability of the plasmid carrying the NDM-5encoding gene was evaluated for all NDM-5-producing E. coli by mating-out assays using the filter-mating method as described previously (23). NDM-5-positive E. coli isolates were used as donors and azide-resistant E. coli J53 strain as recipient.…”

Clinical Molecular and Genomic Epidemiology of Morganella morganii in China

“…Ongoing resistance genes or virulence factors acquisition via mobile genetic elements (MGEs) including integrative and conjugative elements (ICEs) and mobilizable genomic islands (MGIs) has promoted M. morganii to become a new clinical treatment challenge ( Flannery et al, 2009 ; Schultz et al, 2017 ). Resistance genes were mainly plasmid mediated and harbored by various transposons or integrons, such as bla KPC–2 -carrying IncP6 plasmid ( Kukla et al, 2018 ), bla OXA–181 -carrying IncN plasmid ( McGann et al, 2015 ), bla NDM–1 -carrying IncC plasmid ( Aires-de-Sousa et al, 2020 ), bla NDM–5 -carrying IncX3 plasmid ( Guo et al, 2019 ), bla IMP–27 -carrying Tn 7 transposon ( Walkty et al, 2018 ), bla CTX–M–3 -carrying Tn 6741 transposon ( Luo et al, 2020 ), cfr -carrying Tn 7 transposon ( Chen et al, 2019 ) and bla GES–5 -carrying In 1390 integron ( Moura et al, 2018 ), which have significantly contributed to the increased levels of resistance in M. morganii .…”