Developing Non-Antibiotic Options to Manage Mycoplasma Bovis
Project Title
A Screen for Drugs That Reveal Mycoplasma Bovis to the Bovine Immune System
Researchers
Antonio Ruzzini and Murray Jelinski (Western College of Veterinary Medicine) antonio.ruzzini@usask.ca
| Status | Project Code |
|---|---|
| Completed January, 2025 | ANH.01.19 |
Background
Mycoplasma bovis (also called Mycoplasmopsis bovis) is involved in bovine respiratory disease, and mycoplasma treatments are estimated to cost the beef industry $30 to $50 per head. M. bovis also causes significant welfare (lameness) problems. Resistance to current therapies is a growing concern and there is no effective vaccine for M. bovis available.
Most bacteria have a cell wall, but M. bovis only has a cell membrane. That makes it difficult to treat, because many antibiotics are designed to disrupt cell walls, not cell membranes. These researchers explored molecules that may be able to inhibit M. bovis by interfering with its cell membrane and/or inhibit its growth.
Objectives
- Screen for compounds that disrupt cell membrane integrity and inhibit M. bovis.
- Identify membrane drug targets in M. bovis.
What they DID
They used two biochemical screens to measure the impact of ~3,000 potential drug compounds on the M. bovis cell membrane. M. bovis and each potential drug were incubated with a fluorescent dye that binds DNA but cannot cross the cell membrane. If the potential drug was able to make the M. bovis cell membrane permeable, then the dye could enter the cell, bind the DNA and create a fluorescent signal that could be detected in the lab. The same library of compounds was also screened to determine whether they could inhibit M. bovis growth. Compounds that could increase cell permeability and/or inhibit M. bovis were identified and their activities were validated. They also checked for harmful effects on animal cells.
What They Learned
They identified and validated 7 compounds that could disrupt M. bovis cells without killing them. Many of these were inexpensive surfactant compounds, but one was an anti-inflammatory human asthma treatment drug (montelukast sodium) that could also make M. bovis cells more permeable.
They also identified 4 antibiotics, including one called ebselen (and several related compounds) that may have potential for M. bovis drug development. None of these are “off-the-shelf” solutions for M. bovis treatment yet, though. For example, in some cases, the “dose” required to harm M. bovis also had harmful effects on animal cell cultures. Additional medicinal chemistry would be required to improve their antibiotic activities and reduce potential harmful effects on the animal. This work has also identified several membrane-associated proteins that may play important roles in how M. bovis interacts with cattle.
What It Means
This drug repurposing effort has identified several new compounds that have potential for further development as therapies to manage and mitigate M. bovis in cattle.