Our focus is on identifying effective alternatives to traditional antimicrobials to prevent or treat R. equi pneumonia. The rationale for this approach is that we believe that microbes are evolving resistance to existing antimicrobials rapidly. One approach for prevention and treatment is to leverage the exquisitely regulated immune response of the host. We are doing this using 2 strategies: 1) vaccination; and, 2) host-directed immunomodulation.
Currently, our vaccine development is based on collaboration with the laboratory of Dr. Gerald Pier of the Harvard Medical School to use a synthetic polysaccharide conjugated to tetanus toxoid to prevent R. equi foal pneumonia and the disease known as strangles in horses, caused by the bacterium Streptococcus equi subspecies equi. This strategy is exciting not only because of our success with preventing R. equi pneumonia in foals using this vaccine but also because of Dr. Pier’s innovative strategy of a broad-spectrum vaccine. The results of these studies will not only benefit the health of horses, but also people and other animals.
The concept of using host-directed immune responses to protect against infection is motivated by infections such as rhodococcal pneumonia in foals and tuberculosis in people for which an effective vaccine is lacking and for which emergence of resistance by the antibiotics commonly used for treatment represents a major threat. We are investigating agonists of pattern recognition receptors of the innate immune system as a preventative or therapeutic (with or without concurrent antimicrobial treatment) against R. equi pneumonia in foals.
For over 30 years, the class of antimicrobials known as macrolides (in combination with rifampin) has been the standard of care for foals with R. equi pneumonia. Having contributed to furthering our knowledge of the emergence and mechanism of resistance of R. equi (an effort lead by our collaborator Steeve Giguère of the University of Georgia), we are keenly aware of the need for alternative antimicrobials. To this end, we have continued Dr. Martens’s pioneering work with gallium maltolate as an antimicrobial against R. equi, in collaboration with Dr. Lawrence Bernstein. We also have initiated collaborations to explore the use of silver-based products delivered topically to the lungs using novel delivery systems in collaboration with Dr. Carolyn Cannon of the College of Medicine, Texas A&M University. Finally, in collaboration with Drs. Agueda Vargas and Leticia Gressler of the Federal University of Santa Maria in Brazil, we have demonstrated the ability of the compound chloroquine to kill R. equi. We hope to evaluate the clinical effectiveness of these drugs. Having alternative antimicrobial agents available to veterinarians might help reduce the prevalence of resistance to the macrolide antibiotics.
