The discovery began with an “aha” moment by then-Ph.D. candidate Patrick Pearson, who was working in Rich’s lab, along with graduate student Adam Lynch. Pearson, co-author of the paper, is now a NEWVEC post-doctoral researcher at UMass Amherst. Lynch, lead author, is now a research fellow in the Department of Veterinary and Animal Sciences .
Tumor cells and Borrelia burgdorferi , the corkscrew-shaped bacterium that causes Lyme disease, share an unusual feature about the way they grow, Pearson noted and pondered. “It turns out that cancer cells and Borrelia both rely solely on glycolysis for their metabolism,” Rich explains.
Glycolysis, in turn, is dependent on one molecule called lactate dehydrogenase, or LDH. Pearson wondered whether LDH inhibitors, which are used as drug therapies to target certain cancers, might also be an effective strategy against Lyme disease.
“It was a very clever idea,” Rich says. “In principle, we thought these LDH inhibitors should work well to inhibit the growth of Lyme disease bacteria.”
And in fact, in in vitro experiments, they did. “…a range of commercially available LDH inhibitors with various mechanisms of action and origins were tested on Borrelia in Culture,” the paper states. “Of these inhibitors, gossypol, AT-101, and oxamate substantially impacted B. burgdorferi growth in vitro and represent promising candidates against Borrelia infections in vivo .”
Rich says the research will continue at NEWVEC, which was funded by the Centers for Disease Control and Prevention last year with a $10 million award to prevent and reduce tick- and mosquito-borne diseases in New England. NEWVEC aims to bring together academic communities, public health practitioners, residents and visitors across the Northeast, where Lyme infections are concentrated.
“These experiments were done outside of hosts. Now we need to carry this out in mouse models and, eventually, in people,” Rich says.
The researchers note that this drug therapy may also be effective against another tick-borne disease, babesiosis, a malaria-like infection. “This has the potential to kill two birds with one stone,” Rich says. “And that makes this discovery even more tantalizing.”
Pathogens
Experimental study
Cells
Lactate Dehydrogenase Inhibitors Suppress Borrelia burgdorferi Growth In Vitro
22-Jul-2023
The authors declare no conflict of interest.