New superbug gene resistant to the last defence of antibiotics found in China

A form of bacteria that is highly resistant to antibiotics has been found to be widespread among pigs and patients in South China including strains with epidemic potential, according to new research.

The study, published in The Lancet Infectious Diseases, say that a gene called mcr-1 enables bacteria to be highly resistant to polymyxins, the last line of antibiotic defence currently available. The mcr-1 gene was found on plasmids, mobile DNA that can be easily copied and transferred between different bacteria, suggesting an alarming potential to spread and diversify between different bacterial populations.

These are extremely worrying results, says the study’s author Professor Jian-Hua Liu from South China Agricultural University in Guangzhou, China. “Our results reveal the emergence of the first polymyxin resistance gene that is readily passed between common bacteria such as Escherichia coli and Klesbsiella pneumoniae, suggesting that the progression from extensive drug resistance to pandrug resistance is inevitable,” Liu explains.

During routine testing of food animals for antimicrobial resistance in China, Liu and his colleagues isolated an E. coli strain from a pig on an intensive pig farm in Shanghai that showed resistance to colistin that could be transferred to another strain. This prompted the researchers to collect bacteria samples from pigs at slaughter across four provinces, and from pork and chicken sold in 30 open markets and 27 supermarkets across Guangzhou between 2011 and 2014.

They also analysed bacteria samples from patients presenting with infections to two hospitals in Guangdong and Zhejiang provinces. Samples were tested for antibiotic susceptibility and the mcr-1 gene using polymerase chain reaction (PCR) and sequencing.

The researchers found a high prevalence of the mcr-1 gene in E. coli isolates from animal and raw meat samples. The proportion of positive samples increased from year to year, says the team. The mcr-1 gene was also found in 16 E. coli and K. pneumoniae isolates taken from more than 1,300 hospitalised patients.

The researchers also note that the transfer rate, or the rate at which the mcr-1 gene is copied and transferred between different bacteria, was very high between E. coli strains. They also found that the mcr-1 gene has the potential to spread into other epidemic pathogenic bacterial species such as K. pneumoniae and Pseudomonas aeruginosa, which can cause a variety of diseases from pneumonia to serious blood infections, suggesting that mcr-1 is likely to spread rapidly into human pathogens.

The emergence of mcr-1 heralds the breach of the last group of antibiotics, the researchers say. They warn that although the condition is currently confined to China, mcr-1 is likely to emulate other resistance genes such as blaNDM-1 and spread worldwide. “There is a critical need to re-evaluate the use of polymyxins in animals and for very close international monitoring and surveillance of mcr-1 in human and veterinary medicine,” the researchers say.

This study establishes the connection between the agricultural use of colistin and its resistance in slaughtered animals, food and in human beings, according to David Paterson and Patrick Harris from the University of Queensland in a comment.

Colistin is an antibiotic approved in the late 1950s for the treatment of acute and chronic infections caused by certain sensitive strains of Gram-negative bacteria. While healthcare providers had largely stopped using it in the 1970s because of its toxicity, colistin is increasingly being used today to treat severe, bacterial infections, particularly among intensive care-based patients.

One of the few solutions to uncoupling these links is the limitation or cessation of colistin use in agriculture, they say. “This will require substantial political will and we call upon Chinese leaders to act rapidly and decisively. Failure to do so will create a public health problem of major dimensions,” the two added.

China is one of the world's largest users and producers of colistin for agriculture and veterinary use. Worldwide, the demand for colistin in agriculture is expected to reach almost 12,000 tonnes per year by the end of 2015, rising to 16,500 tonnes by 2021.

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