Plasmid-mediated colistin resistance in animals: current status and future directions

Abstract

Colistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene, mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission of mcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA, mcr-1-positive Escherichia coli isolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.

MCR-1 Confers Cross-Resistance to Bacitracin, a Widely Used In-Feed Antibiotic

“…Extensive usage of colistin in food animals is deemed a major driving force for the emergence and transmission of the mcr-1 gene (1, 2, 3). Although limiting colistin usage in animal production (2, 3) is likely the most straightforward approach to mitigate transmissible colistin resistance, a non-colistin usage factor(s) contributing to the persistence and transmission of mcr-1 gene may also exist in complex ecosystems (4). In the United States, despite lack of colistin usage in food animals, mcr-1 -positive Escherichia coli strains were still isolated from swine intestinal samples (5).…”

“…Since the discovery of MCR-1 in 2016 (1), at least five MCR-1 homologues have been identified (4). In this study, we focused only on MCR-1 because MCR-1 is still the predominant determinant of transmissible colistin resistance (4).…”

“…In this study, we focused only on MCR-1 because MCR-1 is still the predominant determinant of transmissible colistin resistance (4). At present, there is a worldwide trend to limit colistin usage in animal husbandry to protect public health.…”

“…At present, there is a worldwide trend to limit colistin usage in animal husbandry to protect public health. However, simply limiting or banning the use of colistin in animal production may not fully solve this serious and challenging antibiotic resistance issue; several potential non-colistin usage risk factors for colistin resistance have been identified and were discussed in a recent review (4). The findings from this study suggest that imprudent and extensive usage of bacitracin in food animals is a non-colistin usage risk factor for transmissible colistin resistance.…”

Antimicrobial resistance: from basic science to translational innovation

“…Sun et al (2018) provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. More importantly, on the basis of published information, Sun et al (2018) discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in animal production system, which include co-selection of mcr-1 with specific clinical antibiotics, factors enhancing horizontal gene transfer (HGT), cross-resistance between colistin and other antimicrobial peptides, and existence of novel colistin resistant genes in ecosystem. Addressing the knowledge gaps identified in this review is imperative to prevent and control transmissible colisitin resistance in animal production in the USA and other countries.…”