Novel Approach Targets Tuberculosis

Mycobacterium tuberculosis, the highly infectious bacterium that causes tuberculosis, is one of the world’s most deadly pathogens. It strikes HIV-positive individuals particularly hard and is becoming increasingly resistant to antibiotics.

Two UNL School of Veterinary Medicine and Biomedical Sciences researchers – Ofelia Barletta-Chacon, physician and microbiologist, and Raul Barletta, biochemist and microbiologist – are taking a novel approach to develop new antibiotics and a vaccine against tuberculosis in humans, particularly people with AIDS, and in animals.

One-third of the world’s population is infected with TB, which kills nearly 2 million people annually. Multidrug-resistant and extensively drug-resistant strains are much deadlier.

Most antibiotics target a single enzyme to inhibit TB so a single mutation can render treatment ineffective. The researchers’ goal is to develop antibiotics that target multiple enzymes to improve effectiveness. "We focus on pathways that have not been investigated to a great extent," Barletta said.

One challenge is that TB bacilli can remain dormant in people without symptoms until aging, HIV or immunosuppressive therapies, such as cancer treatment, activate them. "Eliminating latent bacilli is one of the hardest problems," Barletta said.

"But we think we can attack that with some of the metabolic pathways that we’re studying."

This work, funded by National Institutes of Health grants, may also lead to a more effective vaccine.

Mycobacterial diseases, including Johne’s disease and bovine tuberculosis, also infect cattle and can be economically devastating for owners of infected herds. These researchers hope their work leads to vaccines to prevent bovine TB and tools for more accurate, faster diagnoses in the field.

Their research also may eventually help combat other diseases, such as Crohn’s disease in people, in which mycobacteria have been implicated as potential causative agents.

"We want to find an integrated approach to mycobacterial diseases in humans and animals so we can apply the knowledge of one to another," Barletta-Chacon said.