A protein complex currently explored in cancer treatments may also slow the growth of tuberculosis (TB) bacteria, according to a study from Cornell University’s College of Veterinary Medicine. Researchers discovered that the GID/CTLH protein complex, previously known for helping combat cancer by regulating glucose metabolism, can inhibit the growth of Mycobacterium tuberculosis (Mtb) in immune cells, a breakthrough that could lead to dual-purpose drugs for cancer and TB.
The research team, led by David Russell, professor of infection biology, found that the GID complex allows immune cells infected with Mtb to better resist the bacteria, which contributes to the body’s antimicrobial defense. Their findings, published Oct. 29 in Nature Communications, suggest that therapies aimed at the GID complex for cancer might also be adapted to target TB infections.
“The GID complex is already under investigation for cancer treatments,” Russell said. “If drugs that inhibit this complex can also slow TB, we may have new opportunities for developing TB therapies.”
The study was co-authored by Craig Altier, professor of population medicine at Cornell, and Christopher Sassetti from the University of Massachusetts’ Chan Medical School. The team utilized CRISPR-Cas9 gene-editing to inactivate random genes within mouse immune cells, focusing on those genes that enabled Mtb-infected macrophages to survive. Through this screening, they identified 259 genes associated with infection resistance, including the five subunits forming the GID complex.
In addition to TB, researchers found that disabling the GID complex also helped cells control growth of Salmonella, indicating that the GID complex’s role in infection resistance may apply across multiple bacterial infections.
Russell’s lab is also pursuing chemical screening to find compounds that could replicate the GID knockout effect, a process that could yield potential drug candidates. “Genetic screening gives us scientific insight, but chemical screening can provide compounds for drug development,” Russell explained. Such chemicals could bolster current TB treatments, especially as Mtb increasingly shows resistance to standard drugs.
Russell plans to follow developments in cancer research on the GID complex to potentially repurpose emerging drugs for TB therapy, with hopes that this approach could bring forward new treatment options for patients.
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