New gene for bacterial resistance defeats 'the last class of antibiotics'

Scientists have discovered a new gene, mcr-1, that enables bacteria to be highly resistant to polymyxins, the last line of antibiotic defense. The gene was widespread in enterobacteria—including strains with epidemic potential—sampled from pigs and patients in south China, according to a study published online November 18, 2015, in The Lancet Infectious Diseases.

“These are extremely worrying results. The polymyxins (colistin and polymyxin B) were the last class of antibiotics in which resistance was incapable of spreading from cell to cell,” said study author Jian-Hua Liu, PhD, Professor from South China Agricultural University in Guangzhou, China.

Dr. Liu and colleagues were performing routine testing of livestock for antimicrobial resistance when they recovered an E. coli strain (SHP45) from a pig in an industrial pig farm in Shanghai in July 2013. This strain showed resistance to colistin and demonstrated that it could transfer easily to another E. coli strain.

“Until now, colistin resistance resulted from chromosomal mutations, making the resistance mechanism unstable and incapable of spreading to other bacteria,” Dr. Liu said.

This discovery prompted the researchers to collect bacteria samples from pigs at slaughterhouses across four provinces, and from pork and chicken sold in 30 open markets and 27 supermarkets across Guangzhou between 2011 and 2014. They also analyzed bacteria samples from patients presenting with infections to two hospitals in Guangdong and Zhejiang provinces.

The researchers found a high prevalence of the mcr-1 gene in E. coli isolates from animal (166 of 804) and raw meat samples (78 of 523). The mcr-1 gene was also found in 16 E. coli and K. pneumoniae isolates taken from 1,322 hospitalized patients. To add to this concern, the proportion of positive samples increased from year to year.

Also of concern, the mcr-1 gene was copied and transferred between E. coli strains at a very high rate. Moreover, the researchers found that the mcr-1 gene has the potential to spread into other epidemic pathogenic bacterial species, which indicates that mcr-1 is likely to spread rapidly into human pathogens.

“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 pan-drug resistance is inevitable,” Dr. Liu said.

Study co-author Timothy Walsh, PhD, Professor in the Institute of Infection and Immunity at the University of Cardiff, in Cardiff, UK, told the BBC News website, “If MRC-1 becomes global, which is a case of when not if, and the gene aligns itself with other antibiotic resistance genes, which is inevitable, then we will have very likely reached the start of the post-antibiotic era. At that point if a patient is seriously ill, say with E. coli, then there is virtually nothing you can do.”

In the study, the authors wrote, “The emergence of mcr-1 heralds the breach of the last group of antibiotics. Although 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.”

In an accompanying commentary in The Lancet Infectious Diseases, David Paterson, MBBS, PhD, and Patrick Harris, MBBS, from the University of Queensland, in Brisbane, Australia, wrote, “The links between agricultural use of colistin, colistin resistance in slaughtered animals, colistin resistance in food, and colistin resistance in human beings are now complete. One of the few solutions to uncoupling these connections is limitation or cessation of colistin use in agriculture. 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.”

Study co-author Jianzhong Shen, PhD, from China Agricultural University, in Beijing, China, said, “In response to the rapid increase in colistin-resistant bacteria from animals in China, the Ministry of Agriculture, China, has immediately responded by launching a risk assessment on use of colistin in animal feed additives. This responsible and positive reaction is a reflection on how seriously the Chinese government is taking these findings. We are also working very closely with the Government to assess the impact of mcr-1.”

Dr. Shen added, “It should be also be noted that China is not the only country to use colistin in farming but there are many countries, including in Europe, that use polymixins in agriculture, and therefore the responsibility to acknowledge and address the use of antibiotics across human and veterinary sectors must be also global.”