Molecular characteristics of chromosome-mediated colistin resistance in foodborne Salmonella isolates in China

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Abstract
Objective: To determine the molecular characteristics and mechanisms of colistin-resistant (COLr) Salmonella isolates from 1224 chicken samples in Shanghai, China, between January 2021 and January 2022. Methods: Antimicrobial susceptibility testing, site-directed mutagenesis, RT-qPCR, and lipid A analysis was conducted to investigate the mechanisms of colistin resistance in Salmonella. Results: A total of 268 Salmonella isolates were obtained from chicken samples and 41 isolates were resistant to colistin. The uncommon extensively antimicrobial-resistant Salmonella Muenster was the predominant serotype, accounting for 87.8% (36/41) of the COLr isolates. Most (95.1%, 39/41) of the COLr isolates exhibited amino acid substitutions in the PmrAB. Ten different substitutions in PmrAB were identified, with Val161Gly (n = 14) and Gly206Glu (n = 10) in PmrB being the most prevalent. Four substitutions (Thr147Ser, Phe203Ser, Gly206Glu, and Asp250Tyr) in PmrB have not been reported before and were considered novel mutations. Additionally, it was demonstrated that these substitutions upregulated pmrE and pmrK expression, resulting in the production of L-Ara4N, which modified the lipid A and resulted in an 8–64-fold increase in the colistin MIC (2–8 mg/L). Finally, the deletion of pmrE or pmrK in mutants showed MIC values comparable to parental strains (0.25 mg/L), which suggested that colistin resistance may be conferred through the pmrE and pmrK pathways. Conclusions: These findings illustrate the complex molecular mechanisms of colistin resistance in Salmonella, and the amino acid substitutions in PmrAB are the predominant molecular mechanisms. It is essential to implement monitoring and control measures for colistin resistance.
Funding Information
  • The National Natural Science Foundation of China (32172316)

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