Drug-resistant gene goes from pig farms to patients worldwide

March 27, 2018, University College London
Credit: University College London

A troublesome gene that is resistant to an antibiotic often used as a last resort has been tracked from its origins on Chinese pig farms to hospital patients worldwide in a new study led by UCL and Peking University People's Hospital.

The study, published in Nature Communications, found that the , 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 speed at which mcr-1 spread globally is indeed shocking," said the study's lead author, Professor Francois Balloux (UCL Genetics, Evolution & Environment).

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 , it has now become widely prescribed in the clinic as a last-line drug for infections such as E. coli and Klebsiella pneumoniae.

"Mcr-1 provides relatively low , and mcr-1 strains can still be treated with colistin, but at far higher doses, which is obviously detrimental to the patients as colistin is fairly toxic. I wouldn't be surprised if we saw the emergence and spread of elements that provide higher resistance to colistin than mcr-1, which would make the situation even worse," said Professor Balloux.

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.

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.

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.

Hospitals worldwide are struggling with increasing incidence of hard-to-treat . 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.

"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," said Professor Balloux.

"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," he added.

"Our study highlights the value of analysing DNA sequenced from hundreds of resistant bacteria to track the spread of dangerous resistance genes around the world. By deciphering the genetic code of these bacteria we found it was possible to predict not only how and where but also when mcr-1 started to spread. This is so important as the presence of mcr-1 across the globe, in many different bacteria species, all within only a decade highlights the ease and speed with which these resistant genes can be disseminated," said co-author Dr. Lucy van Dorp (UCL Genetics, Evolution & Environment).

"Our work suggests that mcr-1 was already distributed worldwide just a decade after its emergence on a mobile genetic element. While we don't know the exact transmission routes it spread by, we can presume that other AMR genes will be spread in a similar way, emphasizing that AMR is a truly global problem requiring coordinated international action," added co-author Liam Shaw (UCL Genetics, Evolution & Environment).

Explore further: Bacteria resistant to last-resort antibiotic, missed by standard tests

More information: The global distribution and spread of the mobilized colistin resistance gene mcr-1 Nature Communications DOI: 10.1038/s41467-018-03205-z

Related Stories

Bacteria resistant to last-resort antibiotic, missed by standard tests

March 6, 2018
Emory microbiologists have detected "heteroresistance" to colistin, a last-resort antibiotic, in already highly resistant Klebsiella pneumoniae, a bacterium that causes blood, soft tissue and urinary tract infections.

Team reveals high prevalence of bacteria that carry gene mcr-1 in ecosystem

December 7, 2017
A research collaborative recently found that bacteria that carry the colistin resistance gene mcr-1 commonly exist in food and environmental samples collected from Hong Kong and the Chinese mainland. The mcr-1 gene is a new ...

Researchers discover novel colistin resistance gene mcr-3 in Escherichia coli

June 27, 2017
Researchers have now discovered a new mobile colistin resistance gene, mcr-3, in E. coli of pig origin. The novel mcr-3 gene was discovered when a colistin-resistant Escherichia coli isolate tested negative for both mcr-1 ...

Multi-drug resistant bacteria in China

January 28, 2017
The mcr-1 gene—a gene that makes bacteria resistant to colistin, an antibiotic of last resort, and that is transferrable between bacteria—has been found in a wide variety of strains of Escherichia coli in China following ...

Octapeptin: 'Forgotten' antibiotic offers hope against worst superbugs

January 25, 2018
An antibiotic overlooked since its discovery 40 years ago could help develop new drugs against life-threatening infections caused by some of the world's most dangerous superbugs.

ECDC rapid risk assessment outlines actions to reduce the spread of the mcr-1 gene

June 17, 2016
The recently recognised global distribution of the mcr-1 gene poses a substantial public health risk to the EU/EEA. The gene is widespread in several continents and has been detected in bacteria isolated from multiple different ...

Recommended for you

PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds

December 6, 2018
Although relatively rare in the United States, and accounting for fewer than 5 percent of tuberculosis cases worldwide, TB of the brain—or tuberculosis meningitis (TBM)—is often deadly, always hard to treat, and a particular ...

Silicosis is on the rise, but is there a therapeutic target?

December 6, 2018
Researchers from the CNRS, the University of Orléans, and the company Artimmune, in collaboration with Turkish clinicians from Atatürk University, have identified a key mechanism of lung inflammation induced by silica exposure, ...

Infectivity of different HIV-1 strains may depend on which cell receptors they target

December 6, 2018
Distinct HIV-1 strains may differ in the nature of the CCR5 molecules to which they bind, affecting which cells they can infect and their ability to enter cells, according to a study published December 6 in the open-access ...

Protecting cell powerhouse paves way to better treatment of acute kidney injury

December 6, 2018
For the first time, scientists have described the body's natural mechanism for temporarily protecting the powerhouses of kidney cells when injury or disease means they aren't getting enough blood or oxygen.

New study uncovers why Rift Valley fever is catastrophic to developing fetuses

December 5, 2018
Like Zika, infection with Rift Valley fever virus can go unnoticed during pregnancy, all the while doing irreparable—often lethal—harm to the fetus. The results of a new study, led by researchers at the University of ...

Study highlights potential role of bioaerosol sampling to address airborne biological threats

December 5, 2018
As a leading global city with a high population density, Singapore is vulnerable to the introduction of biological threats. Initiating an early emergency response to such threats calls for the rapid identification of the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.