A team of Chinese healthcare researchers has found a new way to solve one of the mysteries behind a long-standing long-term health hazard.
The scientists could potentially help with a cure for tuberculosis (TB) infection in the future by slowing or stopping TB from becoming resistant to new antibiotics.
Thanquiline is a drug that some TB patients take to control their disease. It works by stopping the infection from becoming resistant by blocking a key TB protein that is found in infected blood. It is widely used as a treatment for malaria.
In the study, Dr Bei Zhang, a nephrologist at the National Hospital for Allergy and Lung Disease, and colleagues found that glioblastoma (brain cancer) was sensitive to the drug in mice with the therapy.
“With our latest work, we’ve identified a new signaling pathway that inhibits the fast-growing TB bacteria,” said Dr Zhang.
“These findings have great potential to accelerate the application of existing TB drug discovery and development, and therefore allow us to find new ways to reactivate dormant TB bacteria to fight infections in people and reduce the potential development of resistance. We believe we can develop an effective approach on the next level toward development of new TB drug against bacteria or against human immune system,” he said.
Taking a novel approach to scientific discovery, the scientists used a novel genetically modified mouse model of TB, expressing different and yet very similar protein-encoding genes on the surface of quiescent TB bacteria.
“We looked for signal receptor proteins expressed on the surface of bacteria that might interfere with drug-discovery or treatment,” explained co-lead author Dr Zhang, who is currently completing a PhD in Immunology at the National Hospital for Allergy and Lung Disease, at the National Institutes of Health.
The team of experts studied a so-called Wnt-ase, an enzyme that catalyzes cell division. The researchers observed that the Wnt-ase is expressed in many epithelial types of bacterial TB, including those that had not previously been associated with the disease.
“We identified the Wnt-s drug-encoding gene in epithelial cells from people living with tuberculosis (TB), as well as in bacterial skin,” said co-lead author Dr Shao-Ying Dong, also at the National Hospital for Allergy and Lung Disease.
The team then showed that the Wnt-secreting TB bacteria had a higher rate of cell division compared to other TB bacteria. The Wnt-induced cell division was not only observable in the context of intact B cells, it was also detectable in mice with an acute myeloid leukodystrophy-like disorder.