Edinburgh Infectious Diseases
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Antibiotic-resistance gene goes from pig farms to patients worldwide

The mcr-1 gene, that confers resistance to antibiotics of last resort, has been tracked from its origins on Chinese pig farms to hospital patients worldwide in a new study involving researchers from University College London, University of Edinburgh and Peking University People's Hospital.

Litter of piglets

The new study, published in Nature Communications, found that the mcr-1 gene, now present across the globe, can be tracked to a single event around 2005 when it moved from pigs into pathogens that affect humans.

The mcr-1 gene makes bacteria resistant to colistin, which is one of the very few drugs effective against multi-drug resistant infections. Colistin was discovered in the 1950s but has until recently been mostly used in pig farming due to its severe side-effects.  With the recent increase in antibiotic resistance, it has now become widely prescribed in the clinic as a last-line drug for infections such as E. coli and Klebsiella pneumoniae.

"The speed at which mcr-1 spread globally is indeed shocking.

Professor Francois BallouxDepartment of Genetics, Evolution & Environment, University College London

Although Mcr-1 provides relatively low resistance to colliston, meaning that strains containing the mcr-1 gene can still be treated with colistin, far higher doses are required than in the past.  This is detrimental to the patients as colistin can bcome toxic at these higher doses. 

Antibiotic resistance spread from Chinese pig farms

The mcr-1 gene is mobile and plasmid-borne, meaning it can be transported from one bacterium to another, even of two different species, and confer resistance to colistin. It was identified in China in 2016, followed by a rapid realisation that it had already spread globally, but its exact origin and spread had not yet been determined.

The research team compiled an exhaustive dataset of 457 mcr-1 positive genome sequences isolated from humans and farm animals from five continents, by sequencing the genomes of 110 bacterial strains and systematically mining previously deposited genomic data from publicly available databases.

Thamarai-Dorai Schneiders in the Dvision of Pathway Medicine at the University of Edinburgh, who was part of the study said

They analysed this data with novel computational tools to show there had been a single emergence of mcr-1, reliably dated to the mid-2000s and which happened likely in Chinese pig farms. They also reconstructed how the mcr-1 element had been spreading globally and to various bacterial pathogens by hitchhiking with various bacterial mobile genetic elements.

Need for improved global surveillance of antibiotic resistance

Lucy van Drop and Liam Shaw, two other members of the team explained that the study highlights the value of analysing DNA sequenced from hundreds of resistant bacteria to track the spread of dangerous resistance genes around the world.

This work represents the first reconstruction of the emergence and spread of an antibiotic resistance element and opens new avenues for improved global surveillance of antibiotic resistance using genomic tools.

"There is no consensus yet on the importance of antimicrobials in livestock being a main driver of the antimicrobial resistance public health crisis. That said, the use of antimicrobials in agriculture is not only a scientific issue but also a societal and economic issue that will need to be addressed.  Given the dearth of new antibiotics in the pipeline, our best hope to avert the current public health crisis is to improve stewardship of existing drugs, by harnessing the potential of bacterial genome sequencing and translate it into improved surveillance and diagnostics tools.

Professor Francois BallouxDepartment of Genetics, Evolution & Environment, University College London

Hospitals worldwide are struggling with increasing incidence of hard-to-treat antibiotic-resistant bacterial infections. The World Health Organisation has been raising the alarm over a post-antibiotic era where minor infections could routinely become untreatable. Public Health England predicts that antibiotic resistance could lead to 10 million deaths every year globally by 2050 and to £66 trillion in lost productivity to the global economy.

While the exact transmission routes by which the mcr-1 element spread are still not known, other AMR genes are likely to be spread in similar ways.  With AMR, we are facing a truly global challenge - the need for robust and coordinated, international action is now required more than ever.

Dr Thamarai Dorai-SchneidersDivision of Infection and Pathway Medicine, University of Edinburgh

Source - University College London