The spread of carbapenem- and polymyxin-resistant Enterobacteriaceae poses a significant threat to public health, challenging clinicians worldwide with limited therapeutic options. This review describes the current coding and noncoding genetic and transcriptional mechanisms mediating carbapenem and polymyxin resistance, respectively.

BackgroundMobile colistin resistance (mcr) genes modify Lipid A molecules of the lipopolysaccharide, changing the overall charge of the outer membrane.Results and discussionTen mcr genes have been described to date within eleven Enterobacteriaceae species, with Escherichia coli, Klebsiella pneumoniae, and Salmonella species being the most predominant. They are present worldwide in 72 countries, with animal specimens currently having the highest incidence, due to the use of colistin in poultry for promoting growth and treating intestinal infections. The wide dissemination of mcr from food animals to meat, manure, the environment, and wastewater samples has increased the risk of transmission to humans via foodborne and vector-borne routes. The stability and spread of mcr genes were mediated by mobile genetic elements such as the IncHI2 conjugative plasmid, which is associated with multiple mcr genes and other antibiotic resistance genes. The cost of acquiring mcr is reduced by compensatory adaptation mechanisms. MCR proteins are well conserved structurally and via enzymatic action. Thus, therapeutics found effective against MCR-1 should be tested against the remaining MCR proteins.ConclusionThe dissemination of mcr genes into the clinical setting, is threatening public health by limiting therapeutics options available. Combination therapies are a promising option for managing and treating colistin-resistant Enterobacteriaceae infections whilst reducing the toxic effects of colistin.

Tweet: "molecular screening of patient samples collected at a national reference laboratory in Pretoria shows endemicity of carbapenemases and rarity of mcr colistin resistance genes" Impacts: Carbapenems and colistin are the last resort antibiotics available for the treatment and eradication of multidrug resistant gram-negative bacteria. Resistance in these antibiotics threaten the public health as it reduces the efficacy of these therapeutics. Klebsiella pneumoniae was identified to harbour all the identified carbapenemases. This is of concern as K. pneumoniae has a history of causing outbreaks and being endemic in healthcare facilities in South Africa. It is important to understand how common carbapenem and colistin-resistant GNB are in the healthcare facilities, as it identifies areas that require attention.

Background:  Mobile colistin resistance (mcr) genes modify Lipid A molecules of the lipopolysaccharide, changing the overall charge of the outer membrane. Methods: A systematic review of all studies published between January 2015 to July 2021 was performed. Included articles described mcr genes in the context of their genetic environment, fitness cost, crystal structure, their enzymatic activity and the risk factors associated with the acquisition of mcr. Studies describing the epidemiology of mcr genes and novel therapeutics were included.Results and Discussion: Ten mcr genes have been described to date within eleven Enterobacteriaceae species, with Escherichia coli, Klebsiella pneumoniae, and Salmonella species being the most predominant. They are present worldwide in 72 countries, with human specimens currently having the highest incidence. This is due to the wide dissemination of mcr in livestock animals, meat, manure, the environment, and wastewater samples, increasing the risk of transmission via foodborne, zoonotic, and vector-borne routes to humans. The stability and spread of mcr genes were mediated by mobile genetic elements such as the IncHI2 conjugative plasmid, which is associated with multiple mcr-variants and other antibiotic resistance genes. The cost of acquiring mcr is reduced by compensatory adaptation mechanisms. MCR proteins are well conserved via structurally. Hence, MCR-1 inhibitors and therapeutics should be applicable to all MCR proteins.Conclusion: Mcr genes have spread from animals into the clinical setting, threatening public health. Combination therapies are a promising option for managing and treating colistin-resistant Enterobacteriaceae isolates whilst reducing the toxic effects of colistin.