Identification of Carbapenemase within Class 1 Integron Structure in Intrinsically Colistin-resistant Enterobacteriaceae

Identification of carbapenem resistance genes in intrinsically colistin-resistant Enterobacteriaceae (ICRE), i.e., Proteus spp., Providencia spp., Serratia spp., and Morganella spp., is necessary for preventing such life-threatening bacteria. Here, we characterized carbapenemase resistance genes and their carriage within class 1 integron structures in clinical intrinsically colistin-resistant Enterobacteriaceae.

Clinical samples were collected from six general hospitals in Tehran and Torbat-e-Heydarieh, Iran, from 2018 to 2020. The isolates were identified by standard microbiological techniques and 16s rRNA sequencing. The resistance to imipenem and colistin was determined by disk diffusion and minimum inhibitory concentration (MIC) assays. PCR-sequencing was performed to detect primary carbapenemase-encoding genes, including blaOXA-48, blaIMP, blaVIM, blaKPC, and blaNDM.

Three Proteus mirabilis, three Providencia stuartii, and two Serratia marcescens isolates were identified. The MICIMP values of all isolates were >16 µg/ml. The blaVIM-1 gene and blaKPC-2 genes were detected in five and four isolates, respectively. Cassette arrays consisting of blaVIM-1-aacA7-dhfrA1-aadA1were detected in five isolates and aadB in one isolate. The blaVIM-1 gene in all blaVIM-1 positive isolates was located on class 1 integrons, while the blaKPC-2 carriage was not related to these genetic elements. The in silico analysis of the large plasmids carrying blaVIM-1-aacA7-dhfrA1-aadA1 array belonging to the IncA/C incompatibility group showed transmissibility among Enterobacteriaceae members.

  Transferable plasmid harboring blaVIM-1 in ICREs can pose a severe threat to public health. More investigations are required to depict the epidemiology of these underestimated carbapenem-resistant Enterobacteriaceae members.