First Report in the Americas of S. enterica Var. Enteritidis Carrying blaNDM-1 in a Putatively New Sub-Lineage of IncC2 Plasmids

Abstract

Background: Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates.

Case report: We studied a patient who, after being discharged from an ICU, developed salmonellosis caused by an antibiotic-susceptible S. enteritidis. After undergoing treatment with ciprofloxacin, the patient presented an episode of asymptomatic bacteriuria originated by a carbapenem and ciprofloxacin-resistant S. enteritidis.

Results: Whole genome sequencing analysis revealed that both Salmonella isolates belonged to the same strain, and that isolate SEn_T2 acquired a plasmid carrying both bla_NDM-1 and qnrA1 genes (pIncCSEn) which was previously present in the patient's gut in at least one Enterobacter cloacae isolate. Additionally, pIncCSEN was identified as a putatively new sub-lineage of IncC2 plasmids which lacked the first copy of the methyltransferase gene dcm and the rhs gene. The resistance genes bla_NDM-1 and qnrA1 were incorporated into a Tn21-derived transposon that included a complex class 1 integron whose genetic arrangement was: intI1- dfrA12- orfF- aadA2- qacEΔ1-sul1-ISCR1- trpF- ble- bla_NDM-1 (in reverse direction)- ISAba125-ISCR1- qnrA- cmlA1- qacEΔ1-sul1.

Conclusions: Antimicrobial persistence and co-selection of antibiotic resistance play an important role in the dissemination of antimicrobial resistance genes; in this regard, a joint effort involving the infection control team, effective antibiotic stewardship, and genomic surveillance could help mitigate the spread of these multidrug resistant microorganisms.

Keywords: NDM-1; Salmonella enterica; antimicrobial resistance; carbapenemases; transposon.

Figure 1

Nucleotide Identity analysis of type 2 IncC plasmids. The innermost circle corresponds to pIncCSEn. The different features are depicted in their corresponding DNA strand (violet arrows: CDS; cyan blocks: repeat regions; magenta blocks: miscellaneous features; orange blocks: miscellaneous RNA). The remaining plasmids are depicted as concentric circles. Filled blocks correspond to regions of homology. The image was generated using the Proksee webpage (https://proksee.ca/) [23].

Figure 2

Evolutionary relationships of IncC plasmids. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (500 replicates) are shown next to the branches. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. The blue-shaded box corresponds to type-1 IncC plasmids, the green-shaded box corresponds to type-2 IncC plasmids, and the yellow-shaded box corresponds to a putative sub-lineage of IncC plasmids (the star indicates the plasmid described in this work).

Figure 3

Linear map of ARI-A in pIncCSEn, compared with the original structure of Tn21. Homologous segments are shown as grey blocks as indicated in the reference.