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

Abstract

Mobile colistin resistance (mcr) genes (mcr-1 to mcr-10) are plasmid-encoded genes that threaten the clinical utility of colistin (COL), one of the highest-priority critically important antibiotics (HP-CIAs) used to treat infections caused by multidrug-resistant and extensively drug-resistant bacteria in humans and animals. For more than six decades, COL has been used largely unregulated in the poultry sector in low- and middle-income countries (LMICs), and this has led to the development/spread of mcr gene-containing bacteria (MGCB). The prevalence rates of mcr-positive organisms from the poultry sector in LMICs between January 1970 and May 2023 range between 0.51% and 58.8%. Through horizontal gene transfer, conjugative plasmids possessing insertion sequences (ISs) (especially ISApl1), transposons (predominantly Tn6330), and integrons have enhanced the spread of mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8, mcr-9, and mcr-10 in the poultry sector in LMICs. These genes are harboured by Escherichia, Klebsiella, Proteus, Salmonella, Cronobacter, Citrobacter, Enterobacter, Shigella, Providencia, Aeromonas, Raoultella, Pseudomonas, and Acinetobacter species, belonging to diverse clones. The mcr-1, mcr-3, and mcr-10 genes have also been integrated into the chromosomes of these bacteria and are mobilizable by ISs and integrative conjugative elements. These bacteria often coexpress mcr with virulence genes and other genes conferring resistance to HP-CIAs, such as extended-spectrum cephalosporins, carbapenems, fosfomycin, fluoroquinolone, and tigecycline. The transmission routes and dynamics of MGCB from the poultry sector in LMICs within the One Health triad include contact with poultry birds, feed/drinking water, manure, poultry farmers and their farm workwear, farming equipment, the consumption and sale of contaminated poultry meat/egg and associated products, etc. The use of pre/probiotics and other non-antimicrobial alternatives in the raising of birds, the judicious use of non-critically important antibiotics for therapy, the banning of nontherapeutic COL use, improved vaccination, biosecurity, hand hygiene and sanitization, the development of rapid diagnostic test kits, and the intensified surveillance of mcr genes, among others, could effectively control the spread of MGCB from the poultry sector in LMICs.

Keywords: One Health; low- and middle-income countries; mcr gene; mobile colistin resistance; poultry sector; tigecycline resistance.

Figure 1

Plasmid-mediated colistin resistance mechanism in Gram-negative bacilli. Mobile colistin resistance (mcr) genes encode MCR proteins, which are cytoplasmic phosphoethanolamine (pEtN) transferase enzymes that modify lipid A by adding pEtN, resulting in a less negative net charge on the bacterial outer membrane, like the chromosomal pathways. Created with BioRender.com (accessed 29 May 2023).

Figure 2

Possible sources and routes of transmission of mcr-gene-containing bacteria (MGCB) originating from the poultry sector to the One Health triad (human–animal–environment) in low- and middle-income countries. Created with BioRender.com accessed on 22 May 2023.

Figure 3

Distribution of mobile colistin resistance (mcr) gene-bearing organisms in poultry meat production and supply chains of low- and middle-income countries, 1970 to May 2023. : Poultry bird; : poultry meat; : egg; : poultry feed; : persons in contact with poultry bird/poultry product; : poultry environment (litter/manure, sewage, vectors, soil, or water). This map was created with https://www.mapchart.net/ (accessed on 30 May 2023).