Epidemiology and Traits of Mobile Colistin Resistance (mcr) Gene-Bearing Organisms from Horses

Abstract

Mobile colistin resistance (mcr) genes (mcr-1 to mcr-10) threaten the efficacy of colistin (COL), a polymyxin antibiotic that is used as a last-line agent for the treatment of deadly infections caused by multidrug-resistant and extensively drug-resistant bacteria in humans and animals. COL has been used for more than 60 years for the prophylactic control and treatment of infections in livestock husbandry but not in horses. Polymyxin B is used for the prophylactic control and empirical treatment of infections in horses without conducting sensitivity tests. The lack of sensitivity testing exerts selection pressure for the acquisition of the mcr gene. By horizontal transfer, mcr-1, mcr-5, and mcr-9 have disseminated among horse populations globally and are harbored by Escherichia coli, Klebsiella, Enterobacter, Citrobacter, and Salmonella species. Conjugative plasmids, insertion sequences, and transposons are the backbone of mcr genes in the isolates, which co-express genes conferring multi- to extensive-drug resistance, including genes encoding extended-spectrum β-lactamase, ampicillinase C, fosfomycin, and fluoroquinolone resistance, and virulence genes. The transmission of mcr genes to/among bacterial strains of equine origin is non-clonal. Contact with horses, horse manure, feed/drinking water, farmers, farmers’ clothing/farm equipment, the consumption of contaminated horse meat and its associated products, and the trading of horses, horse meat, and their associated products are routes for the transmission of mcr-gene-bearing bacteria in, to, and from the equine industry.

Antimicrobial Resistance and Extended-Spectrum Beta-Lactamase Genes in Enterobacterales, Pseudomonas and Acinetobacter Isolates from the Uterus of Healthy Mares

“…It is currently recognized that mares and their reproductive environment are a source of origin of different microorganisms, which can be disseminated to other animals and to humans through direct and indirect contact [ 40 , 51 ].…”

“…Likewise, the use of broad-spectrum cephalosporins could be a selection factor for bacteria with ESBL. Generally, the resistance genes that code for the expression of this ESBL phenotype, such as bla CTX-M, bla SHV , bla TEM , and bla CTX-M , are in plasmids or integron-type structures, which would facilitate horizontal gene transfer [ 30 , 40 , 66 , 87 , 88 , 89 , 90 ].…”

“…Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa were classified by the World Health Organization (WHO) as critically important pathogens [ 32 ] and are among the main antimicrobial resistance (RAM) threats in humans [ 33 , 34 ] and animals [ 35 , 36 , 37 , 38 , 39 ]. These situations are a cause of concern for the medical environment due to the probable dissemination of microorganisms and the limitation of therapeutic options [ 40 ]. The objective of this study was to determine the antimicrobial resistance and extended-spectrum beta-lactamase genes in Enterobacterales , Pseudomonas spp., and Acinetobacter spp.…”

Mobile Colistin Resistance (mcr) Gene-Containing Organisms in Poultry Sector in Low- and Middle-Income Countries: Epidemiology, Characteristics, and One Health Control Strategies

“…The emergence and spread of plasmid-mediated transmissible COL resistance genes, specifically mobile COL resistance (mcr) genes mcr-1 to mcr-10, first reported in late 2015, threaten the clinical efficacy of COL in veterinary and human medical practices [25]. Unfortunately, mcr-gene-bearing plasmids (especially conjugative plasmids) spread through inter-and intraspecies horizontal gene transfer (HGT) at lightning speed among Gram-negative bacilli (GNB) [23,26]. mcr genes have numerous variants and subvariants, which have been identified in isolates/samples from humans, animals, and environments across over 70 countries on all continents [27].…”

“…This attachment of the pEtN moiety abolishes the negative charges on lipopolysaccharide (LPS) to which cationic COL/polymyxins have an affinity, thereby resulting in COL resistance [18] (Figure 1). The cocarriage of mcr with plasmid-encoded genes conferring resistance to fluoroquinolones and other last-resort HP-CIAs, such as genes encoding flavin monooxygenenases (TetX) and resistance-nodulation-drug efflux pumps (TmexCD-toprJ) (which mediate resistance to tigecycline), carbapenemases (which mediate resistance to carbapenems), extended-spectrum β-lactamases (ESBLs) and plasmidic ampicillinase C (pAmpC) (which mediate resistance to extended-spectrum cephalosporins), and glutathione S transferase (which mediate resistance to fosfomycin) is of further concern because such strains could become XDR or pandrug-resistant (PDR) in a single event of HGT, which could result in nearly untreatable infections, fatalities, and huge economic losses [26]. Unfortunately, plasmids carrying mcr genes with other last-resort antimicrobial determinants seem to be more stable, giving carriers a greater fitness advantage and enabling the easier and more rapid transfer of genes [29].…”