Genetic Characterization of Multidrug-Resistant Salmonella Typhimurium Carrying Mcr-1 in China

Abstract Background: With the rapid emergence of plasmid mediated polymyxin resistance gene mcr-1, multidrug-resistant Salmonella caused great troubles in clinical treatment and attracted extensive attention. Here we report multidrug-resistant Salmonella strains harboring mcr-1 in China, which are resistant to both polymyxin, traditional antibiotics and even clinically wide-used antibiotics. Methods: We screened 1454 strains of Salmonella collected in our laboratory from 2006 to 2018 from 3 provinces or regions for mcr-1 by PCR. Antimicrobial susceptibility testing was determined. Plasmid conjugation assays were carried out to analysis the transferability of polymyxin resistance. Genetic polymorphism analysis of Salmonella was performed using the PFGE, and the plasmid profiles were characterized by S1-PFGE and southern blotting. The plasmids harboring mcr-1 were sequenced and compared. Results: Eleven S. Typhimurium isolates harboring mcr-1 with polymyxin resistance (MICs 4μg/ml) were identified from intestinal infections and foods in China. All S. Typhimurium isolates were multidrug-resistant to traditional antibiotics and even clinically wide-used antibiotics. Three types of plasmids harboring mcr-1 were recovered (IncHI2, IncX4 and IncI2). Compared with the reference plasmid, IncX4 and IncI2 plasmids had extremely similar typical backbone, and contain only mcr-1 resistance gene. However, IncHI2 were the most diverse type of plasmid due to containing a large MDR region, including blaCTX-M, oqxB, sul, aph, aadA and blaTEM. IncHI2 plasmids were observed to contain only one or no insertion sequence ISApl1 around mcr-1, without forming a circular intermediate. Conclusion: With the horizontal transfer of different types of plasmids, mcr-1 is widely spread worldwide. These prevalent plasmids are responsible for resistance to polymyxin, traditional antibiotics and even clinically wide-used antibiotics resulting from transmission of mcr-1 and other resistance genes. Our studying emphasizes the necessity to jointly monitor its international epidemic and preemptive further upgrade.