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UTHSC’s Brian Peters, PhD, Receives $1.5 Million Grant for Research on Vaginitis Pathogenesis

Dr. Brian Peters (Photo by Connor Bran/UTHSC)

Brian M. Peters, PhD, assistant professor in the Department of Clinical Pharmacy and Translational Science in the College of Pharmacy at the University of Tennessee Health Science Center (UTHSC), has been awarded a four-year $1,520,000 grant for his research into the molecular pathways through which Candida albicans, or C. albicans, elicits inflammation during vaginitis.

Long believed to result from immunodeficiency, a growing body of evidence strongly suggests that vaginitis is now considered to be an immunopathology, in which the host response actually drives disease symptoms. Under this project entitled, “Candidalysin: a key mediator of Candida vaginitis immunopathology,” Dr. Peters and his lab have been working to understand how a newly described fungal toxin Candidalysin majorly contributes to the pathogenesis of vulvovaginal candidiasis, also known as a genital yeast infections.

“Lack of a comprehensive understanding of the host and fungal factors that initiate symptomatic disease remains a barrier to progress in better treating and managing this most prevalent human fungal infection,” Dr. Peters said. “We published a paper that showed if you use strains of C. albicans that lack this specific virulence factor that, even though they colonize just fine, they are incapable of causing inflammation; so, this factor seems really important in driving symptoms associated with the disease.”

Among the above observations, Dr. Peters and his team looked at numerous C. albicans vaginal clinical isolates and noticed that there is one structure of Candidalysin that is identical to the sequence strain (a strain used by many researchers worldwide to do genetic manipulation and cloning work), and a whole separate group of isolates who have an alternate protein sequence.

“We took the sequence strain and deleted Candidalysin, so that it could no longer express any of this virulence factor. We then engineered this strain to express either the sequence strain-like or alternate toxins,” said Dr. Peters. “What we were able to see is that there is a significant decrease in the ability to cause inflammation with this variant.”

The goal of this grant is to tease out what specific changes between these molecules cause reduced inflammation and also to look at how changes in the promoter (parts of genes responsible for regulation) alter expression levels with the ultimate goal of identifying promising new pathways that may be exploited for the clinical management of vaginitis. This award also builds off of previous NIH funding of Dr. Peters’ research to examine downstream effectors that regulate inflammatory events in the host with the hope that these pathways may be altered to alleviate symptomatic disease.

“In the first year of this grant, we’d like to definitively show that this alternate protein has reduced activity in terms of eliciting inflammation and which specific amino acids contribute to that reduced inflammation activity or affect its cellular processing.”