It's estimated that nearly one-third of the world's population (more than two billion people) are infected with Mycobacterium tuberculosis (TB). According to the World Health Organization, 5 per cent to 10 per cent of the infected people eventually develop active TB, and can transmit the bacterium to others.
Almost two million die from the disease each year. But the current treatment regimen for the disease is long and arduous, making patient compliance difficult. As a result, some strains of the bacteria have become resistant to many or all of the available antibiotics.
In a paper published in Cell Host & Microbe journal today (November 17), a team of researchers has shown that M. tuberculosis and several of its close relatives, including M. marinum , exploit a family of host enzymes known as ABL-family tyrosine kinases to gain entry into host cells and to survive once inside. The researchers also showed that the imatinib drug, an Abl-family inhibitor, limits infection, and works just as well against antibiotic resistant strains. Also, when given alongside traditional front-line antibiotics, the drugs worked synergistically to enhance their effectiveness.
The bottom line: by targeting the host — not the bacteria itself — researchers were able to reduce the host's mycobacteria load, and even target antibiotic-resistant strains, all while enhancing the effectiveness of front-line antibiotics.
“This study implicates host tyrosine kinases in entry and intracellular survival of M. tuberculosis and M. marinum and suggests that imatinib may have therapeutic efficacy against tuberculosis,” says Daniel Kalman, PhD, lead investigator of the study. Kalman is associate professor of pathology in Emory University School of Medicine. Imatinib is known commercially as Gleevec and is already FDA approved.
