A new study by a team of British and Chinese researchers suggests that the colistin-resistance gene MCR-1 began to emerge almost a decade before it was first identified, and likely originated in Chinese livestock.
The gene, which was first identified in Escherichia coli isolates from Chinese pigs, pork products, and patients in November 2015, has since been reported in food-producing animals and people in more than 30 countries across five continents. Its rapid dissemination is a major public health concern because colistin is a last-resort antibiotic reserved for multidrug-resistant infections. As a result, public health officials have called for more surveillance to detect pathogens carrying the gene.
MCR-1's spread has been aided by its location on plasmids, which are mobile pieces of DNA that can be shared among bacteria. When these free-floating genetic elements move on to other types of bacteria, that means that bacteria that have never been exposed to colistin now have the ability to resist it. Furthermore, MCR-1-carrying plasmids have been found to carry other antibiotic-resistance genes, raising the specter of bacterial infections that are nearly impossible to treat.
But while MCR-1 has emerged as a global health threat in the past 2 years, a reconstruction of the gene's evolution indicates the global spread has not been as sudden as it appears.
Analysis reveals when MCR-1 became mobilized
In the non-peer reviewed study, published on the pre-publication web portal bioRxiv, the researchers compiled a global dataset of 457 sequenced MCR-1-positive bacterial isolates, including 110 newly sequenced isolates from China.
The isolates came from 31 countries, with China (212 isolates) and Vietnam (58) having the most MCR-1–positive samples. Nearly 90% of the isolates (411) were E coli, but isolates carrying the gene were found in seven other bacterial species: Salmonella enterica, Klebsiella pneumoniae, Escherichia fergusonii, Kluyvera ascorbata, Citrobacter braakii, Cronobacter sakazakii, and Klebsiella aerogenes.
Using the whole-genome sequencing data, the researchers then conducted a phylogenetic analysis to reconstruct the evolutionary history of the MCR-1 gene and how it became mobile.
What they found, by focusing on the genetic context surrounding the MCR-1 sequence, was that the isolates shared a common background that took shape in 2006, when MCR-1 first became mobilized as part of a composite transposon—a mobile segment of DNA that can move from one location on the genome to another. This was followed by a dramatic demographic diversification and expansion, as the MCR-1 transposon jumped to different plasmids.
The researchers also observed that the highest proportion of isolates carrying transposon sequences similar to the ancestor that emerged in 2006 were environmental and agricultural isolates from China, where colistin was used widely in food-producing animals until 2016. "This pattern is in line with agricultural settings acting as the source of mcr-1 within bacteria isolated from humans," the authors of the study write.
They go on to suggest that a likely driver for the ensuing global spread of MCR-1-carrying bacteria is trade of food animals and meat, although movement of colonized humans may be playing a role as well.
The authors say the findings are consistent with retrospective surveillance data, which has found the presence of MCR-1 in samples dating back to 2005 in Europe. But while the current study suggests a date for when MCR-1 became a mobile gene, "The origin of mcr-1 prior to its mobilization remains elusive," they write.
More important, they believe that their research highlights how scientists can use sequencing data to better understand how antibiotic resistance genes evolve and spread. "We hope that future efforts relying on more sophisticated computational tools and even more extensive genetic sequence data will become part of the routine toolbox in infectious disease surveillance," they conclude.
Nov 17 bioRxiv study