๐ โ๐๐๐๐๐๐๐๐ข๐ ๐๐๐ข๐: Innovative Approaches to Combat Antibiotic-Resistant Infections ย
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Rhodococcus equi (R. equi) is a leading cause of pneumonia and death in foals less than 6-months-old worldwide. Initial exposure to R. equi occurs through contact with the soil and contaminated farm environment. In farms where the bacteria are endemic, morbidity rates can reach up to 40%. Importantly, the threat of infection can also be extended to immunocompromised people. The economic losses caused by R. equi are attributed to the lengthy, potentially expensive treatment of infected foals, and guarded prognosis for those severely affected, making R. equi a significant problem for the equine industry worldwide. The lack of vaccines to prevent R. equi infections in horses forces treatment to rely solely on antibiotics. This reliance on antibiotics is precarious, as R. equi has demonstrated a remarkable ability to adapt and develop resistance against antibiotics. Moreover, antibiotic use can induce adverse side effects in foals, including antibiotic-associated diarrhea and hyperthermia. These concerns highlight the pressing need to develop antibiotic-alternative strategies to treat R. equi infections and reduce the risk of antibiotic resistance.
The Helmy Laboratory at the University of Kentucky Maxwell H. Gluck Equine Research Center, in Lexington, is dedicated to developing novel drugs as antibiotic alternatives to improve foal health and welfare through better control of R. equi. We have identified novel drug candidates that show promising efficacy when evaluated in the laboratory against R. equiโs growth, biofilm formation, virulence, colonization and survivability in the alveolar macrophages (the bacteriaโs target cells within the foal). These pharmacologically active compounds, identified using innovative technologies, offer a multifaceted approach to infection control.
The identified drugs originated from two different sources: small molecules extracted from natural products isolated from subterranean environments in Appalachian Kentucky by the UKโs Center for Pharmaceutical Research and Innovation and novel probiotic strains that had not been previously tested for their effect against pathogenic bacteria. Probiotics are well known for their beneficial effects on the host, enhancing gut health and immunity and directly impacting bacterial growth. As a result, these newly discovered small molecules and probiotics could potentially treat R. equi-associated pneumonia in foals and control bacterial contamination of the environment by fecal shedding. The next step is to continue the evaluation of the efficacy and potential toxicity of these drug candidates in the laboratory. Once these potential treatments are deemed safe, we will translate these laboratory findings into real-life using foals as animal models and evaluate the efficacy of the identified drug candidates in protecting foals from infection and stopping the shedding of bacteria to the environment.
The Helmy Labโs goal is to continue developing novel drugs that benefit the entire equine industry by controlling R. equi and other bacterial infections in foals, as well as the spread of diseases within the farm environment. By decreasing the use of antibiotics and preventing their adverse effects, we can help prevent the spread of multi-drug resistant R. equi, promote sustainable horse agriculture and health and reduce economic losses by the equine industry in the U.S. and worldwide.
This project is a collaboration between the Helmy Lab, the UK Martin-Gatton College of Agriculture, Food and Environment and the Thorson Lab at the UK College of Pharmacy. The evaluation of the selected new drug candidates in vitro is supported by the American Quarter Horse Foundation and the Center of Biomedical Research Excellence for Translational Chemical Biology.
Editorโs note: This is an excerpt from Equine Disease Quarterly, Vol. 31, Issue 3, funded by underwriters at Lloydโs, London, brokers, and their Kentucky agents. It was written by Yosra A. Helmy, DVM, MVSc, PhD, assistant professor of infectious diseases and microbiology at the University of Kentuckyโs Gluck Equine Research Center, in Lexington.ย ย
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