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Cathelicidin and Swine dysentery
Do cathelicidins contribute to neutrophils defenses in swine dysentery?
Infectious diseases are increasingly untreatable due to the worldwide rise of antibiotic resistance. Developing new non-antibiotic treatments is a priority in both human and veterinary medicine. For pigs, antibiotic resistance in swine dysentery (SD) is particularly troubling. SD is caused by a highly contagious spirochete Brachyspira hyodysenteriae, which colonizes the colon of young pigs to cause colitis and severe hemorrhagic diarrhea. Without treatment, mortality can reach 30% in naturally infected herds. SD is a concerning animal welfare problem for the pork industry, causing decreased production, increased treatment costs and culling of infected animals. Antibiotics largely eliminated B. hyodysenteriae in the 1990s, but antimicrobial resistance has recently caused its resurgence. Current treatments still rely on large amounts of antibiotics that exacerbate resistance, so new therapies stand to greatly benefit the pork industry. Developing new treatments requires an understanding of host immune responses, which remain largely unknown in SD.
This project aims to understand how the porcine gut immune system responds to infection during SD and use this knowledge to evaluate novel therapeutic targets.
Our aims are:
1. Describe the kinetics of neutrophil recruitment (white blood cells that kill bacteria) and cathelicidin expression over the course of B. hyodysenteriae infection, and
2. Determine if treatment with cathelicidins is effective against SD.
We are partnered with Dr. Hancock and his research team at the University of British Colombia, who have developed synthetic peptides derived from natural cathelicidins. These Innate Defense Regulators (IDRs) promise to promote neutrophil recruitment and function while reducing harmful side effects. We aim to evaluate therapeutic activity of these IDRs in SD.
This project has important applications for the pork industry but is also significant for human infectious colitis, since pigs are the closest animal model for humans. Findings from this project have important implications in the fight for alternative treatments against antibiotic-resistant gut infection in humans and animals.
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