The mobilized colistin resistance (mcr-1) gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating gram negative infections. mcr-1 is capable of horizontal transfer between different strains of a bacterial species and after discovery in November 2015 in E. coli (strain SHP45) from a pig in China it has been found in Escherichia coli, Salmonella enterica, Klebsiella pneumonia, Enterobacter aerogenes, and Enterobacter cloacae. As of 2017[update], it has been detected in more than 30 countries on 5 continents in less than a year.
The "mobilized colistin resistance"(mcr-1) gene confers plasmid-mediated resistance to colistin, a polymyxin and one of a number of last-resort antibiotics for treating infections. The gene is found in no less than ten species of the Enterobacteriaceae: Escherichia coli, Salmonella, Klebsiella pneumonia, Enterobacter aerogenes, Enterobacter cloacae, Chronobacter sakazakii, Shigella sonnei, Kluyvera species, Citrobacter species, and Raoultella ornithinolytica. The mcr-2 gene is a rare variant of mcr-1 and is found only in Belgium. Additional variants, mcr-3, mcr-4, and mcr-5, were identified in E. coli and Salmonella.
The mechanism of resistance of the MCR gene is a phosphatidylethanolamine transferase. The enzyme transfers a phosphoethanolamine residue to the lipid A present in the cell membrane of gram-negative bacteria. The altered lipid A has much lower affinity for colistin and related polymyxins resulting in reduced activity of the antimicrobial. This type of resistance is known as target modification.
Discovery and geographical spread
The gene was first discovered in E. coli (strain SHP45) from a pig in China April 2011 and published in November 2015. It was identified by independent researchers in human samples from Malaysia, China, England, Scotland, and the United States.
In April 2016, a 49-year-old woman sought medical care at a Pennsylvania clinic for UTI symptoms. PCR of an E. coli isolate cultured from her urine revealed the mcr-1 gene for the first time in the United States, and the CDC sent an alert to health care facilities. In the following twelve months, four additional people were reported to have infections with mcr-1 carrying bacteria.
As of February 2017[update] mcr-1 has been detected in more than 30 countries on 5 continents in less than a year, and it appears to be spreading in hospitals in China. The prevalence in five Chinese provinces between April 2011 and November 2014 was 15% in raw meat samples and 21% in food animals during 2011–14, and 1% in people hospitalized with infection.
Given the importance of mcr-1 in enabling bacteria to acquire polymyxin resistance, MCR-1 (the protein that is encoded by mcr-1) is a current inhibition target for the development of new antibiotics. For example, ethylenediaminetetraacetic acid, a metal-chelating agent, was shown to inhibit MCR-1 as it is a zine-dependent enzyme. Substrate analogues, such as ethanolamine and glucose, were also shown to inhibit MCR-1. The use of a combined antibiotics regime has shown to be able to overcome the resistance that is caused by mcr-1, although the mechanism of action may not be directly targeting the MCR-1 protein.
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