Tuberculosis, a bacterial infection primarily of the lungs that leads to wasting and respiratory distress, has been feared throughout human history and remains so today. It is responsible for the deaths of more people than any other single infectious disease. According to the World Health Organization, globally more than 10 million people become sick with tuberculosis each year and one in six will die from the infection. In addition to those with active disease, more than a quarter of the global population is estimated to be infected with the bacterium but maintain it in a dormant state. This latent infection can convert to active disease if immune function declines due to advanced age or HIV infection.
From 1884, when he established the first laboratory in the United States dedicated to research on tuberculosis, Dr. Edward Livingston Trudeau and his protégés pioneered treatment of the dread disease, culminating in antibiotic treatments that led to a cure by the 1950s. This cure, however, has remained lengthy and complex, requiring a minimum of six months of treatment on four different potentially toxic drugs. In much of the world, this treatment is challenging to deliver properly, and incomplete treatment can lead to the emergence of drug-resistant strains. Infections with these drug-resistant strains, now comprising over five percent of new cases, can require over two years to treat with treatment failing in nearly half of cases. In order to turn the tide of the tuberculosis pandemic we must develop new treatments that can effectively eliminate multi-drug resistant bacteria and reduce the treatment time and complexity.
Trudeau scientists are making use of recent developments in our understanding of how tuberculosis bacteria are able to grow and survive in the lungs in order to identify novel treatments to more quickly cure the disease. They are employing new techniques involving genetic manipulation of the bacterium, imaging of the infection within the lungs, computational modeling of protein-drug interactions, whole genome sequencing, and measuring the metabolic state of the bacterium to reveal vulnerabilities that can be exploited in the search for improved treatments.