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The last drug has fallen. Bacteria carrying a gene that allows them to resist polymyxins, the antibiotics of last resort for some kinds of infection, have been found in Denmark and China, prompting a global search for the gene.

The discovery means that gram-negative bacteria, which cause common gut, urinary and blood infections in humans, can now become “pan-resistant”, with genes that defeat all antibiotics now available. That will make some infections incurable, unless new kinds of antibiotics are brought to market soon.

Colistin, the most common polymyxin, is a last-resort treatment for infections with bacteria such as E. coli and Klebsiella that resist all other available antibiotics.


In November, Yi-Yun Liu at South China Agricultural University in Guangzhou and colleagues discovered a gene for resistance to colistin in infected livestock, meat and humans. The mcr-1 gene can pass easily between bacteria, and the researchers predicted it could soon go global.

In circulation

Unknown to them, it already had. After their announcement, Frank Aarestrup of the Danish Technical University in Lyngby immediately searched for the sequence in a Danish database of bacterial DNA sampled from people, animals and food. He found it in one person who had a blood infection earlier this year, and in five bacterial samples from poultry meat imported from Germany between 2012 and 2014.

The poultry could have been raised outside Germany, says Aarestrup – he doesn’t know its origin. But ominously, all the bacteria also carried genes conferring resistance to many other antibiotics, including penicillin and cephalosporins.

“We do not now know where in the world it originated”

The genes found in Denmark and China are the same, says Aarestrup, suggesting mcr-1 has travelled, rather than arising independently in each place. It is thought to have emerged originally in farm animals fed colistin as an antibiotic growth promoter.

Livestock origin

The gene has not yet been found in North America, says Lance Price of George Washington University in Washington DC, but researchers at the Centers for Disease Control and Prevention in Atlanta, Georgia, are now checking genetic databases. One reason for its absence could be that North American livestock farmers use relatively little colistin – although that will not keep the gene from migrating among bacteria.

“We do not now know where in the world it originated,” Aarestrup cautions. His team is now trying to get some idea by collecting information and different strains via existing global and European Union research projects that compile genetic sequences from pathogens.

An origin in China seems most probable as antibiotics are widely fed to animals to promote growth. The bulk of the 12,000 tonnes of colistin fed to livestock yearly around the world is used in China, say Liu and colleagues, which would favour the evolution of mcr-1. Antibiotic growth promoters have been banned in Europe precisely because they promote drug-resistant bacteria. Denmark, ironically, was among the first to ban them.

Worldwide concern

The drugs are still heavily used, however, to treat infections common in crowded livestock barns, such as diarrhoea. In 2012, the World Health Organization called colistin critically important for human health, meaning its use in animals should be limited to avoid promoting resistance. Yet in 2013, the European Medicines Agency reported that polymyxins were the fifth most heavily used type of antibiotic in European livestock.

Colistin is used in both humans and animals in India, says Abdul Ghafur of the Apollo Hospital in Chennai. The country is another hotbed of antibiotic resistance because of weak controls on the drugs. “I have treated colistin-resistant infections,” Ghafur says, and researchers in India plan to test bacterial samples for the gene.

“If mcr-1 is present in India then that will be a disaster,” says Ghafur, who fears it will spread as fast as did genes for resistance to another antibiotic of last resort, carbapenem.

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