Characterization Of Chromosome-Mediated Colistin Resistance In Escherichia coli Isolates From Livestock In Korea

Shukho Kim,1 Jung Hwa Woo,1 Nayeong Kim,1 Mi Hyun Kim,1 Se Yeon Kim,1 Joo Hee Son,1 Dong Chan Moon,2 Suk-Kyung Lim,2 Minsang Shin,1 Je Chul Lee1 1Department of Microbiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2Bacterial Disease Division, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do, Republic of KoreaCorrespondence: Je Chul LeeDepartment of Microbiology, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of KoreaTel +82-53-420-4844Fax +82-53-427-5664Email leejc@knu.ac.krPurpose: Colistin resistance in gram-negative bacteria from humans and livestock has been increasingly reported worldwide. The aim of this study was to investigate the underlying mechanisms of chromosome-mediated colistin resistance in Escherichia coli isolates from livestock in Korea.Materials and methods: Thirty mcr-1-negative isolates were selected from a collection of colistin-resistant E. coli isolates collected from livestock in 2005 and 2015 in Korea. Amino acid alterations in PmrAB, PhoPQ, MgrB, and PmrD were investigated. Colistin-resistant derivatives were produced by serial passage of colistin-susceptible E. coli isolates in colistin-containing media.Results: Thirty colistin-resistant mcr-negative E. coli isolates were classified into 26 sequence types. Twenty-two isolates carried diverse amino acid alterations in PmrB, PhoP, PhoQ, MgrB, and/or PmrD, whereas no mutation in any of these genes was found in the remaining eight isolates. Sixteen out of the 22 isolates shared a total of nine polymorphic positions that were found in colistin-susceptible E. coli strains. Colistin-resistant derivatives from two colistin-susceptible isolates showed the same genetic alterations that were observed in colistin-resistant clinical isolates.Conclusion: Our results suggest that the mechanism underlying chromosome-mediated colistin resistance remain to be discovered in E. coli. Selective pressure of colistin in vitro induced the same genetic mutations associated with colistin resistance in vivo. Efforts to reduce colistin consumption in livestock should be redoubled, to prevent the occurrence of colistin-resistant E. coli strains.Keywords: colistin resistance, two-component system, livestock, genetic mutation, mcr gene