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MCR-1 Gene Secrets Revealed

Researchers from the University of Bristol have revealed the structural and mechanistic basis of transferable colistin resistance conferred by the MCR-1 gene.

Concerning rates of antibiotic-resistant infections continue to increase throughout the world. As such, researchers are hard at work studying the mechanisms involved in conferring this resistance in an attempt to be able to eradicate them.

Recently, researchers from the University of Bristol have provided more insight into how these bacteria are gaining resistance mechanisms; in particular, “how the MCR-1 gene protects bacteria from colistin,” an antibiotic typically only used as a last resort,” according to a press release on their research.

This is not the first time that members of the team have made inroads in the battle against colistin resistance. Jim Spencer, PhD, from the School of Cellular and Molecular Medicine, and colleagues from Oxford, Cardiff, Diamond Light Source, Thailand and China “identified MCR-1 as the first colistin-resistance gene that could be passed between bacteria, enabling resistance to spread rapidly within a bacterial population.”

In 2016, the gene was discovered in human cases throughout the world, including in the United States, where cases were confirmed in Pennsylvania, New Jersey and Connecticut. According to the press release, “the spread of MCR-1 has been linked to agricultural use of colistin, indicating that transmission between animals and humans may take place. In response to these findings the Chinese government has now banned use of colistin in animal feed.”

It was previously discovered that the MCR-1 gene confers resistance to creating a protein that modifies the surface of the bacteria in such a way that colistin is unable to bind to the surface. As this is the mechanism by which colistin works, the gene renders the bacteria colistin-resistant, or more concerning, resistant to the last possible treatment against the infection.

With this in mind, Dr. Spencer and colleagues worked to create detailed images of the protein created by the MCR-1 gene to be able to identify the “key features that are necessary for it to function.” The team used “X-rays produced at Diamond's crystallography beamlines,” and “constructed computer models of the chemical reaction that leads to resistance” to create the images and study the protein.

Professor Adrian Mulholland, co-author of the study and Principal Investigator for the BristolBridge initiative, an EPSRC-funded research initiative at the University of Bristol that aims to engage researchers in the physical sciences and engineering with the problem of antimicrobial resistance, is quoted in the press release as stating, “Our results illuminate the structural and (for the first time) mechanistic basis of transferable colistin resistance conferred by MCR-1, thanks to the combination of biological, chemical and computational expertise brought to bear on this project. We are confident that our findings will drive efforts to understand MCR-1-mediated resistance and ultimately help identify routes towards overcoming MCR-1 activity in harmful bacteria.”

Researchers around the world continue to look into new ways to combat antibiotic resistance and prevent instances of these infections. Recent studies have focused on additional approaches for fighting the infections by targeting a microbe’s essential metal supply and evaluating the potential toxicity of carbon monoxide treatments on the bacteria, among others.

In addition, antibiotic stewardship programs which closely monitor the use of antibiotics continue to grow in healthcare institutions as new methods of implementing them are tested. Humans are not the only animals impacted by these infections and as such, the Food and Drug Administration recently enacted the Veterinary Feed Directive, which stipulates that medically important antibiotics may only be used in animal feeds under the professional supervision of a licensed veterinarian.