A research team based at the UGA College of Veterinary Medicine has discovered a novel gene—erm(46)—that confers antibiotic resistance in Rhodococcus equi, a soil-dwelling bacterium which commonly infects foals and causes opportunistic infections in immunocompromised people. The finding was made in collaboration with researchers at the University of Edinburgh, Texas A&M University, and the University of Washington.
Dr. Steeve Giguère, the Marguerite Thomas Hodgson Chair of Equine Studies and a board-certified large animal internal medicine specialist, led the team, which sequenced the genomes of antibiotic-resistant and antibiotic-susceptible R. equi isolates collected from foals in four states. They searched each isolate’s genome for genes with similar sequences to known genes that cause bacterial resistance to the macrolide class of antibiotics in other bacterial species. Through their search, they discovered a new gene, which was named erm(46) by the Nomenclature Center for MLS Genes at the University of Washington.
When the team cloned erm(46) into susceptible R. equi isolates (those that are normally inhibited by antibiotics), they found that erm(46) induced a high level of resistance to macrolide, lincosamide and streptogramin B antibiotics. Moreover, they found that the gene can be transferred from resistant to susceptible isolates of R. equi during bacterial mating. “This process likely contributes to the spread of resistance,” said Giguère.
Their finding is the first molecular characterization of resistance to these three classes of antibiotics in Rhodococcus equi. “Before, we knew we had resistant isolates, but we did not know how resistance occurred and we had no molecular markers to identify and track the resistant bacteria,” said Giguère.
Rhodococcus equi, a Gram-positive intracellular pathogen, is one of the most important causes of disease in foals between three weeks and five months of age, said Giguère. So far, Giguère and his team have identified antibiotic-resistant R. equi isolates carrying erm(46) in New York, Florida, Texas and Kentucky—where, on one farm producing 100 to 170 foals a year, as many of 40 percent of infected foals were found to carry resistant isolates.
The bacterium is present in soil year-round, but because it typically causes disease only in foals up to five or six months of age, illnesses typically manifest in spring and summer. “It is believed that most foals become infected through inhalation of R. equi within the first few weeks of life, and they start showing clinical signs of pneumonia between three weeks and five or six months of age,” said Giguère.
People may come into contact with Rhodococcus on farms, while gardening, or during other activities that disturb dirt; however, it typically only causes infection in immunocompromised individuals. Not all R. equi causes disease in foals. A piece of DNA located outside the chromosome, called a plasmid, is responsible for making R. equi virulent in foals. Variations on this plasmid can be found in pigs and also cattle.
The spread of drug-resistant Rhodococcus may be a growing problem, said Giguère.
“It’s something that was unheard of 15 years ago, and now we’ve found it in multiple states. We need to conduct a well designed epidemiological study to really know the prevalence of of resistant isolates across the country.”
The team’s study was recently published in the Journal of Antimicrobial Chemotherapy (tinyurl.com/q4kzg5g).
Coauthors on the study include: Londa J. Berghaus, Mary K. Hondalus and Jennifer M. Willingham-Lane from the University of Georgia College of Veterinary Medicine; Elisa Anastasi, Jose A. Vasquez-Boland and Iain MacArthur from the University of Edinburgh; Noah D. Cohen from Texas A&M University; and Marilyn C. Roberts from the University of Washington.
Their work was funded by the Morris Animal Foundation, the largest private funder of companion animal research.