Team lands NIH funds to examine tuberculosis and metabolism

The project is a component of one of four recently announced Tuberculosis Research Units (TBRU), funded with a total of up to $105.3 million over seven years from the NIH National Institute of Allergy and Infectious Diseases (NIAID).

The number of people getting sick or dying from TB worldwide has slowly declined in recent years. Yet global burden remains substantial: About one-third of the world’s population is thought to carry latent TB bacteria, according to the World Health Organization. In 2013, an estimated 9 million people became ill with TB and 1.5 million died from the disease.

The TBRU in which CSU is involved, “Metabolic Factors that Control the Spectrum of Human Tuberculosis,” is expected to receive up to $19.5 million over seven years. The unit will examine how the chronic bacterial infection changes metabolism and why altered metabolism increases TB disease susceptibility.

Discovering new, translational treatments

CSU researchers Randall Basaraba and Brendan Podell, faculty members in the Department of Microbiology, Immunology and Pathology, have already observed that TB results in alterations in glucose and lipid metabolism similar to that of humans.

In this project they will be joined by Adam Chicco, an associate professor in CSU’s Department of Health and Exercise Science and an expert in lipid metabolism. Chicco will help the team understand the link between changes in glucose and lipid metabolism and identify ways to restore metabolism to normal. The new strategies tested by the CSU group will explore whether drugs that are currently used to treat patients with diabetes and cardiovascular disease can also be used in TB patients.

The researchers hope treatments found effective in animals may be translated to human medicine. The project’s co-principal investigator, Megan Murray of the Harvard School of Public Health, will be working with a group of TB patients in Lima, Peru.

Colorado State’s Mycobacteria Research Laboratories are long-standing leaders in TB research. The CSU team has expertise in the use of rodent models of TB alone and TB combined with diabetes, a disease becoming more threatening in low- and middle-income countries.

An important similarity to diabetes

The CSU team recently discovered an important similarity in the metabolic changes involved in TB and diabetes that has opened up new treatment options. The studies will not only help researchers gain a better understanding of why diabetic patients develop more severe and difficult-to-treat TB, but why diabetes is more difficult to control when the two diseases occur together.

“We think that the changes in glucose and lipid metabolism seen in TB and diabetes patients might have a similar cause,” Basaraba said. “Our research will help us understand these similarities and whether drugs used to treat diabetics will also help TB patients.”

He and Podell have found that the metabolic abnormalities become more pronounced in animal subjects that have both diabetes and TB. Murray has demonstrated that human diabetic patients are more likely to develop tuberculosis than non-diabetics, Podell said, adding that the two diseases share important similarities that need to be explored.

“Diabetes is not just a disease related to the Western lifestyle anymore,” he said, noting that one outcome of the project could be identifying the metabolic similarities and differences between diabetes and TB.

Continuing their previous work, Podell and Basaraba aim to identify new therapies that can be used to restore metabolic normalcy and improve the severe TB conditions that can occur among diabetics.

The project will be led by Murray and principal investigator D. Branch Moody of the Brigham and Women’s Hospital in Boston. In addition to Basaraba’s team, collaborators include Partners in Health and geneticist Soumya Raychaudhuri of the Brigham and Women’s Hospital.

The TBRU grant number is U19 AI111224.

Source: Colorado State University