“There are certainly, in the environment, cryptic antibiotic resistance genes that have yet to be transferred to human pathogens,” study coauthor Edward Topp, an environmental scientist at University of Western Ontario, London, and also Agriculture and Agri-Food Canada, tells The Scientist in an email.
Topp and colleagues collected soil samples from farm plots in London, Canada, that the team had exposed to antibiotics for up to 16 years. The researchers extracted DNA from the samples, then cloned fragments of specific sequences into a strain of E. coli sensitive to antibiotics. When the researchers put the altered E. coli in petri dishes with various antibiotics, they saw some colonies were able to grow, indicating the transfected DNA fragments conferred resistance. Through sequencing, they identified 34 new antibiotic resistance genes.
“The particularly surprising result is the discovery of a gene that encodes for an unusual small proline-rich polypeptide that confers resistance to the macrolide antibiotics, very important in human and animal medicine,” Topp says. Macrolide antibiotics are used to treat strep throat and pneumonia, as well as chlamydia and syphilis. The mechanism by which the newly identified gene confers resistance to macrolide antibiotics is not yet known.
With advanced genomic techniques, studies such as Topp’s are helping researchers understand the diversity of resistance compounds in the environment, says bacterial epidemiologist Kimberly Cook of the United States Department of Agriculture. “What we are learning is that the genes that confer resistance are wide ranging and the mechanisms for resistance are even wider ranging than previously thought,” says Cook, who was not involved in the current study.
Microbiologist Rafael Cantón of the Ramón y Cajal Institute for Health Research in Madrid notes that antibiotic resistance genes are naturally present in soil bacteria, and some may work in ways not yet identified in clinical bacteria. “If we understand these resistance mechanisms, we can search for new antibiotics that might not be affected for these mechanisms,” he says in an email to The Scientist.
Indeed, natural environments may serve as hotspots for the evolution of antibiotic resistance, Topp and colleagues write in their study. Farmland, for instance, is exposed to antibiotics by the spread of manure from chicken, pigs, and other livestock, which are often given antibiotics to maintain their health. Human waste, also used as fertilizer, can contain antibiotics as well. A growing number of studies suggest that such dumping animal and human waste and other anthropogenic activities are increasing the abundance of antibiotic resistance genes in the environment, though it’s not clear if pathogens can recruit antibiotic resistance genes through horizontal gene transfer from the environment.
The best way to ensure pathogens can’t recruit antibiotic resistance genes from the environment is by not putting them there in the first place, Topp notes. He suggests a push for continued reduction of antibiotic use in food animal production through regulatory and economic measures, which would reduce the amount of antibiotics that enter into the agricultural system through the spread of manure.
“This is very clear,” writes Cantón. “If we reduce the presence of antibiotics in the environment, we will reduce selection of resistant bacteria. Antibiotics kill or inhibit susceptible bacteria but not resistant ones. Hence, overload of antibiotics in the environment enriches resistant populations.”
C. Lau et al., “Novel antibiotic resistance determinants from agricultural soil exposed to antibiotics widely used in human medicine and animal farming,” Applied and Environmental Microbiology, doi:10.1128/AEM.00989-17, 2017.