Scientists have discovered a compound found in many drugs prescribed for the treatment of glaucoma may also be effective against tuberculosis.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis that most commonly affects the lungs.
The World Health Organization (WHO) estimate that around 2 billion people around the world are infected with TB bacteria, but in most cases the immune system keeps it under control.
But if the immune system becomes weak, then the bacterium gains the upper hand, spreads and causes disease. One strategy that helps it do this is an ability to evade the immune system.
In the journal Antimicrobial Agents and Chemotherapy, the team from Michigan State University (MUS) in East Lansing describes how the sulfa-based compound ethoxzolamide switches off the TB bacterium’s ability to evade the immune system.
They also found the compound reduces disease symptoms in mice.
Senior author Robert Abramovitch, an assistant professor of microbiology, says they found ethoxzolamide stops the TB bacterium from deploying its immune-evasion strategy, effectively “shutting down its ability to grow inside certain white blood cells in the immune system.”
- TB is spread from person to person through the air
- Over 95% of TB cases and deaths are in developing countries
- More than 20% of TB cases worldwide are due to smoking.
TB bacteria are very good at sensing certain cues and adapting to their environment. One such cue is a change in acidity – or pH level – that could herald an attack from the immune system.
“The compound we found inhibits TB’s ability to detect acidic environments,” Prof. Abramovitch explains, “effectively blindfolding the bacterium so it can’t resist the immune system’s assault.”
For the study, he and his colleagues screened 273,000 compounds for any that might be effective against the TB bacterium.
In earlier research, Prof. Abramovitch had developed a fluorescent biosensor that glows green under conditions that mimic TB infection. They used this to screen the compounds.
They ran several tests and showed that “ethoxzolamide reduces M. tuberculosis growth in both macrophages and infected mice.” Macrophages are a type of immune cell that the TB bacterium invades and replicates in.
The team is excited by their find because not only may the compound be able to prevent the spread of TB, it may also shorten the duration of treatment, and thus tackle the problem of drug resistance.
Resistance to standard anti-TB drugs is widespread. The biggest reason for this is because the treatment takes a long time, as Prof. Abramovitch explains:
“It’s difficult for a patient to complete the entire antibiotic course required to kill all of the bacteria. Shortening the duration will help slow the development of these resistant strains.”
He also notes that it is not necessary to kill the bacterium to stop TB. Drugs that give the immune system a boost by blocking the pathogen’s ability to sense and evade the immune system should also be effective.
The National Institutes of Health, AgBioResearch, the Jean P. Schultz Biomedical Research Fund, and MSU startup funds helped finance the study.
Earlier this year, Medical News Today reported a large gene study that found new clues on how the TB bacterium evades the immune system. In the journal Nature Genetics, researchers from the UK and Germany describe how they found variants in the gene ASAP1 on chromosome 8 appear to affect a person’s susceptibility to TB.