Coming Soon: Deadly E. coli?

Physicians and public health officials have long feared complete resistance to antibiotics; and now those fears may have come true. In a study in Lancet Infectious Diseases, researchers have revealed the discovery of a new gene that allows bacteria to become resistant to colistin, considered the “last line of defense” to antibiotic resistance.

The finding is important and potentially devastating, because it is the first to demonstrate that the antibiotic that works when all others fail is not infallible after all. “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,” the study authors cautioned.” Until now, polymyxin resistance has involved chromosomal mutations only, but has not been reported via horizontal gene transfer.

The study began as routine testing for antimicrobial resistance in China, but the results are anything but routine. Researchers isolated an e-coli strain from a pig found to be resistant to colistin. They collected bacteria from pigs from across four provinces, as well as pork and chicken sold in Chinese markets. Following this, they analyzed samples taken from patients presenting with infections in two hospitals.

Through a series of genetic tests and mass spectrometry, the researchers were able to link Polymyxin resistance in animals singularly to the plasmid-mediated MCR-1 gene. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. From there, they identified E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011—14, and 16 (1%) of 1322 samples from patients with infection.

“The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance,” the researchers noted. “Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasize the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.”

The finding calls into question the use of colistin in agriculture. Much more importantly from a global perspective, resistance to all antibiotics, although seen by some as inevitable, would be an immense public concern. Even bacteria now seen as relatively harmless and common would become potentially deadly.