Molecular characterization of IncFII plasmid carrying bla NDM-5 in a Salmonella enterica serovar Typhimurium ST34 clinical isolate in China

Abstract

ABSTRACT The detection rate of carbapenem-resistant nontyphoidal Salmonella (NTS) is relatively low. However, carbapenem-sensitive and carbapenem-resistant Salmonella enterica serovar Typhimurium ( S. enterica serovar Typhimurium) were isolated from a clinical outpatient within a span of 10 days, named 1104–65 and 1104–75. We aimed to reveal the mechanism of carbapenem resistance in S. enterica serovar Typhimurium isolates in this case. The resistance phenotype of S. enterica serovar Typhimurium was analyzed by the VITEK-2 Compact equipment and Kirby-Bauer disc diffusion method. Whole-genome sequencing was used to analyze the serotype, ST type, genetic relationship, resistance genes, plasmid replicon, the genetic environment of bla NDM-5 , and the characteristics of IncFII plasmid carrying bla NDM-5 in S. enterica serovar Typhimurium. The transferability of the IncFII plasmid carrying bla NDM-5 was verified by the conjugation assay and PCR. The serotypes of both NTS are S. enterica serovar Typhimurium, belonging to ST34. Single nucleotide polymorphisms analysis showed that they were the same clone. A conjugative IncFII plasmid pIncFII-NDM5 with transferability was detected in isolate 1104–75, which harboring the bla NDM-5 gene was the primary mechanism responsible for mediating carbapenem resistance in S. enterica serovar Typhimurium. The genetic environment of bla NDM-5 on pIncFII-NDM5 is “IS 26 -ΔIS 3000 -IS 5 -ΔIS Aba125-bla NDM-5 - ble MBL - trpF-dsbC -cutA -IS 26 ”, which was confirmed as a novel structure not previously reported in the NCBI database. Although the mechanism is rarely reported in NTS, the prevalence of IncFII plasmid pIncFII-NDM5 will pose a great threat to the clinical treatment of S. enterica serovar Typhimurium. Meanwhile, the coexistence of bla CTX-M-55 , qnrS1 , bla NDM-5 , and mph(A ) in S. enterica serovar Typhimurium ST34 warrants additional attention. IMPORTANCE In this study, an IncFII plasmid pIncFII-NDM5 carrying bla NDM-5 was found in carbapenem-resistant Salmonella enterica serovar Typhimurium ( S. enterica serovar Typhimurium), which has conjugative transferability and carried bla NDM-5 , ble MBL , mph(A ), and bla TEM-1 four resistance genes that can mediate resistance to multiple antibiotics including cephalosporins, beta-lactamase inhibitor combinations, carbapenems, and macrolides. Phylogenetic analysis showed that 1104–65 and 1104–75 were closely related to other S. enterica serovar Typhimurium in this area. The above-mentioned S. enterica serovar Typhimurium chromosome carries bla CTX-M-55 , qnrS1 , and tet(A ) genes, so the antibiotic resistance of isolates will be further enhanced after obtaining the pIncFII_NDM5-like plasmid. Meanwhile, we discovered a novel genetic structure of bla NDM-5 mediated by the IS 26 composite transposon, which will expand our understanding of the emergence and spread of carbapenem-resistance genes. Altogether, the presence of the IncFII plasmid pIncFII-NDM5 further underscores the need for vigilant surveillance and appropriate infection control measures to mitigate the impact of carbapenem-resistant S. enterica serovar Typhimurium in clinical settings.