‘Disturbing’ drug-resistant superbug gene has been detected in Canada

The alarming drug-resistance gene MCR-1 that was first detected in China in November has been found in meat sold in Ontario in 2010, the Star has learned. The gene grants bacteria like E. coli resistance to colistin, a powerful antibiotic of last resort.

Thestar.com
Jan. 5, 2016
By Jennifer Yang

An alarming new superbug gene that makes bacteria resistant to a last-resort antibiotic has been detected in Canada, the Star has learned.

The gene, called MCR-1, produces an enzyme that makes bacteria invincible to colistin, a highly-toxic antibiotic used only when all other drugs have failed.

MCR-1 was first reported in November by scientists in China, who published a paper in The Lancet that set off alarm bells across the globe. Analyzing bacterial samples in southeastern China, researchers found 260 samples of E. coli with the MCR-1 gene on meat, hospital patients and farm animals - the likely source of this new superbug, the paper suggests.

But the news that really sent a shudder through the scientific community was that MCR-1 is located on a plasmid - a free-floating snippet of DNA that bacteria can easily share, thus spreading the resistance to other organisms.

“It’s clearly the biggest story to come out (in 2015),” said Lance Price, a professor of environmental health at George Washington University, who studies antibiotic resistance. “There have been horrible things all year but this is the most disturbing.”

So far, there have been no reports of deaths caused by MCR-1 and some people could be harbouring the superbug asymptomatically. But the nightmare scenario is that MCR-1 will spread to more virulent bacterial strains that also carry other resistance genes - thus creating a “pan-resistant” superbug capable of defeating every antibiotic in the medicine cabinet.

Since the Lancet paper, at least a dozen other countries have also found the MCR-1 gene. Scientists, looking through databases of bacterial samples, detected the gene everywhere from Denmark and Algeria to Laos.

Among them is Canada, where an investigation was triggered in December by the Public Health Agency of Canada. The Canadian findings have not yet been published but a case report has been submitted to the Lancet, according to Dr. Michael Mulvey, chief of antimicrobial resistance with the PHAC’s lab in Winnipeg.

The superbug gene was found in three different samples of E. coli, all previously collected for special research projects: one from a 62-year-old patient in Ottawa and two from ground beef sold in Ontario.

The Ottawa patient likely picked up the bug in Egypt, where she lived for several years, according to Dr. Baldwin Toye with the Ottawa hospital, who co-wrote a 2013 paper describing her case and four others.

She was hospitalized three days after moving back to Canada and treated for an abdominal infection. Toye believes another pathogen was responsible for her illness, however, and the patient was simply harbouring the MCR-1 gene, which Mulvey discovered retrospectively during his recent investigation.

Meanwhile, the ground beef samples were found nearly a year apart in different locations in Ontario, a butcher shop and a grocery chain, according to Mulvey. Both were collected in 2010 - predating the samples from China, which were collected between 2011 and 2014.

“To see it show up was a surprise for me,” Mulvey said. “It supports that there’s global dissemination of this gene already ... we’re now going to have to look back even prior to (2010), because maybe it’s been around for even longer.”

For scientists worried about antibiotic resistance, the emergence of colistin resistance is troubling but comes as no surprise. Bacteria are naturally equipped with resistance mechanisms, but the overuse - and misuse - of antibiotics has exerted an unnatural pressure on bacteria to evolve. Those that can withstand antibiotics survive and reproduce.

Colistin, which belongs to a group of antibiotics called the polymyxins, was actually discovered in the late 1940s but was quickly shelved due to its highly toxic side effects. Pharmaceutical companies moved on to develop other, better antibiotics — but, one by one, bacteria have evolved strategies for knocking them down.

“We’ve sort of run out of our good drugs,” Price said. “So out of desperation … we have to revive this old drug because it’s all we have left.”

Colistin is still rarely used in human medicine because doctors want to conserve the antibiotic’s effectiveness. But polymyxins are often given to livestock animals to prevent infections and promote growth - especially in China, one of the world’s highest users of colistin in agriculture. (While colistin isn’t used in agriculture in Canada, polymyxin B - a similar compound that creates the same resistance problems as colistin - is.)

In 2015, the global market for colistin in agriculture reached nearly 12,000 tonnes and is expected to rise to 16,500 tonnes by 2012, according to the Lancet paper. “That’s insane,” said Dr. Gerry Wright, a microbiologist with McMaster University and expert in antibiotic resistance.

Scientists have already seen colistin resistance emerge. In Canada, for example, ongoing hospital surveillance stemming back to 2010 has found 13 samples of colistin-resistant bacteria, according to Mulvey.

But MCR-1 is unique in that it’s located on a plasmid which bacteria can share even with different species - the equivalent of a human sharing its DNA with a tree.

“For many years, scientists, including me, have been living under the misapprehension that you could never ever get mobile colistin resistance,” said Timothy Walsh, a microbiologist with Cardiff University who co-authored the initial Lancet paper. “And once it’s mobilized, what tends to happen is it transfers much more quickly.”

Walsh said the Chinese government is taking MCR-1 seriously and he expects it will announce an official ban on colistin use in agriculture.

But microbiologists like Wright, who is now studying MCR-1, would like to see polymyxins banned from agricultural use in every country, including Canada.

“Any antibiotic class used for humans should never be used for animals (unless they’re sick),” he said. “I just find it absolutely mind-boggling that we’re going into 2016 and we’re still having this discussion.”

The emergence of MCR-1

The discovery of the colistin-resistance gene in China was a global alarm bell, sending scientists scrambling to their labs to check for MCR-1 in their own countries. Two months later, it has already been found in 11 other countries, including Canada - and the list will only continue to grow.

China

Nov. 18, 2015: The superbug gene was first reported in The Lancet by researchers in China. Looking at bacteria collected between 2011 and 2014, the researchers found E. coli with MCR-1 on 21 per cent of slaughterhouse pigs and 15 per cent of raw chicken and pork. Sixteen hospital patients also had MCR-1 positive infections. “The effect on human health by mobile colistin resistance cannot be underestimated,” the researchers warned.

Malaysia

Nov. 18, 2015: In their Lancet paper, the authors pointed out that Malaysian scientists had published bacterial DNA sequences in late December 2014 with genes that look like MCR-1 — suggesting the superbug was already in Malaysia too. “The possibility that mcr-1-positive E. coli have spread outside China and into other countries in southeastern Asia is deeply concerning,” they wrote.

Denmark

Dec. 3, 2015: After the announcement from China, Danish researchers searched through their own bacterial data - previously collected under a surveillance program for antibiotic resistance - and found MCR-1 in six samples of E. coli. One was from an elderly patient with prostate cancer who suffered a blood infection in 2015; the other strains were growing on European chicken meat imported between 2012 and 2014.

England and Wales

Dec. 11, 2015: The Chinese announcement also triggers an investigation in the United Kingdom, where public health officials combed through the DNA sequences of more than 24,000 archived bacterial samples. Fifteen had the superbug gene; 13 came from patients and two stemmed from a single piece of poultry meat imported from the European Union. “These findings confirm, although newly discovered, the mcr-1 gene is already present in England and Wales in various bacterial species harboured by the human population,”

The Netherlands, Portugal, Algeria, Laos, Thailand, France

Dec. 17, 2015: The number of affected countries suddenly doubles overnight as The Lancet publishes five letters from researchers around the globe, all announcing that they, too, have detected the MCR-1 gene. It showed up in bacterial samples taken from tourists (in the Netherlands), people (Laos and Thailand), food (Portugal and France), farmers (Laos) and chickens and pigs (Laos and Vietnam). More MCR-1 was also discovered in China - this time recovered from people’s gut bacteria.

Canada

Today: Canada is the latest country to join the MCR-1 club. Government scientists combed through archived samples of bacteria and found three hits that were positive for the superbug gene: one from a human E. coli infection, two from lean ground beef samples. The earliest sample was collected in 2010 and actually pre-dates the China samples that were analyzed in the Lancet report from November.