A Patient With Multiple Carbapenemase Producers Including an Unusual Citrobacter sedlakii Hosting an IncC blaNDM-1- and armA-carrying Plasmid

Abstract

Background. Patients colonized with multiple species of carbapenemase-producing Enterobacterales (CPE) are increasingly observed. This phenomenon can be due to the high local prevalence of these pathogens, the presence of important host risk factors, and the great genetic promiscuity of some carbapenemase genes. Methods. We analyzed 4 CPE (Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, Citrobacter sedlakii), 1 extended-spectrum cephalosporin-resistant K. pneumoniae (ESC-R-Kp), and 1 carbapenemase-producing Acinetobacter baumannii simultaneously isolated from a patient transferred from Macedonia. Susceptibility tests were performed using a microdilution MIC system. The complete genome sequences were obtained by using both short-read and long-read whole-genome sequencing technologies. Results. All CPE presented high-level resistance to all aminoglycosides due to the expression of the armA 16S rRNA methylase. In C. sedlakii and E. coli (ST69), both the carbapenemase blaNDM-1 and armA genes were located on an identical IncC plasmid of type 1a. The K. pneumoniae (ST268) and P. stuartii carried chromosomal blaNDM-1 and blaOXA-48, respectively, while the ESC-R-Kp (ST395) harbored a plasmid-located blaCTX-M-15. In the latter 3 isolates, armA-harboring IncC plasmids similar to plasmids found in C. sedlakii and E. coli were also detected. The A. baumannii strain possessed the blaOXA-40 carbapenemase gene. Conclusions. The characterization of the genetic organization of IncC-type plasmids harbored by 3 different species from the same patient offered insights into the evolution of these broad- host-range plasmids. Moreover, we characterized here the first complete genome sequence of a carbapenemase-producing C. sedlakii strain, providing a reference for future studies on this rarely reported species.

The Use of Long-Read Sequencing Technologies in Infection Control: Horizontal Transfer of a blaCTX-M-27 Containing lncFII Plasmid in a Patient Screening Sample

“…The nearest ancestor plasmid, calculated by BLASTn (Percent Query Coverage: 86%; Percent Identity: 99.95%, for BRIG visualisation see Figure 1 ), was isolated in 2020 in Switzerland (NCBI GenBank accession no. CP071077.1, plasmid p3347558_4) [ 18 ]. Overall, these results strongly suggest horizontal plasmid transfer has occurred between these two strains at one point in the past.…”

Intestinal colonization with multidrug-resistant Enterobacterales: screening, epidemiology, clinical impact, and strategies to decolonize carriers

“…In another study (2008)(2009), transmission from infants colonized with CTX-M-15-Kp during an NICU outbreak to parents/relatives was also observed in 32% of the households [156]. It should also be noted that there are numerous accounts in the literature of colonized patients hospitalized in other institutions (including abroad) who imported MDR-Ent to low-prevalence countries [177][178][179][180][181]. These patients can transmit their MDR-Ent and consequently generate outbreaks.…”

A brief insight into Citrobacter species - a growing threat to public health

“…A number of studies reported that few ANT(3") enzymes, encoded by aadA (aadA1, aadA2, aadA16), conferred resistance to spectinomycin and streptomycin in Citrobacter spp. (Babiker et al, 2020;Ramsamy et al, 2020;Moser et al, 2021;Han et al, 2022;Luo et al, 2022). The presence of streptomycin inactivating genes (strA, strB) was also reported in Citrobacter spp.…”

“…The isolate showed reduced susceptibility to carbapenems, 3 r d and 4 t h -generation cephalosporins, aminoglycoside, trimethoprim-sulfamethoxazole, and colistin (Faccone et al, 2019). Moreover, the bla NDM-1 , found to coexist with armA in the C. sedlakii strain, isolated from the same patient, is another example of conferring resistance to a broad range of antibiotics, including carbapenems and aminoglycosides via horizontal transfer (Moser et al, 2021). Co-existence of bla NDM-1 with bla SHV-12 on the same transferrable IncX3 plasmid pZY-NDM1 in C. freundii and co-production of NDM-1 and OXA-10 in C. braakii isolate on different plasmids was also reported (Zhang et al, 2021;Han et al, 2022).…”

“…In two studies, aminoglycoside resistance caused by target methylation was observed in C. sedlakii and C. portucalensis. This resistance was due to the presence of the armA gene in C. sedlakii and both armA and rmtC genes in C. portucalensis (Moser et al, 2021;Luo et al, 2022). In C. portucalensis, armA were coharbored with aacA4cr, aphA1 bla SHV-12 gene on a separate IncC group plasmid, whereas rmtC gene was coharboured with IncFII : FIB plasmid-borne bla NDM-1 gene (Luo et al, 2022).…”