A drug commonly used to treat glaucoma may also be an effective way to treat even the drug-resistant type of tuberculosis.
A new study shows that ethoxzolamide, a sulfa-based compound found in many prescription glaucoma drugs, actually turns off the TB bacterium’s ability to invade the immune system.
“Basically, ethoxzolamide stops TB from deploying its weapons … shutting down its ability to grow inside certain white blood cells in the immune system,” says Robert Abramovitch, a microbiologist at Michigan State University. “We found the compound reduces disease symptoms in mice.”
Immune system vs. TB
TB may not have eyes and ears, but it has the uncanny ability to sense certain environmental cues in the body and adapt. One of these cues includes the infection’s ability to detect pH—or acidity levels—which tells the disease it’s being attacked by a host immune cell.
“The compound we found inhibits TB’s ability to detect acidic environments, effectively blindfolding the bacterium so it can’t resist the immune system’s assault,” Abramovitch says.
It’s estimated that 2 billion people, globally, carry the infection, but in most cases it lies dormant and the immune system is able to prevent it from spreading in the body.
“It’s a standoff however,” Abramovitch says. “The immune system has difficulty clearing the infection and the TB bacterium is just waiting for the immune system to weaken.”
Needle in the haystack
For the new study, published in the journal Antimicrobial Agents and Chemotherapy , researchers screened 273,000 different compounds in hopes of finding one that could possibly stop the disease.
By using a synthetic biosensor that glows green in response to conditions that mimic TB infection, something developed in earlier research, Abramovitch eventually found the needle in the haystack that turned the bacterium’s sensing ability off.
Further, this elusive compound not only has the potential of preventing the disease from spreading, but it could also help shorten the length of treatment and slow the emergence of drug resistance, particularly if found to work in conjunction with other existing TB drugs. Current treatments can last up to six months.
“The single biggest reason for the evolution of drug-resistant strains is the long course of treatment,” Abramovitch says. “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.”
Trying to kill TB bacteria isn’t the only way of stopping the disease though, he adds.
“We don’t necessarily have to find drugs that kill TB, we just need to find ones that interfere with the bug’s ability to sense and resist the immune system. By giving the immune system a helping hand, natural defenses can then kill the bacteria.”
The National Institutes of Health, MSU startup funds, AgBioResearch and the Jean P. Schultz Biomedical Research Fund, supported the work.
Source: Michigan State University