Tuberculosis (TB) remains one of the most lethal infections in the world, resulting in over 1.5 million deaths each year. While it is currently curable, the bacteria responsible for it are fast evolving resistance to our antibiotics, thwarting attempts to keep the disease under control. Now, scientists have found a new compound that can boost the power of existing antibiotics and even reverse the bugs' resistance.
Tuberculosis is caused by Mycobacterium tuberculosis bacteria, which colonize the lungs. While it can be killed off with a treatment plan of antibiotics, the bacteria won't go down without a fight. Not only do they often develop a genetic resistance to the antibiotics, but they can also band together to form biofilms, which makes it harder for the drugs to do their job.
So the researchers set out to find a way to stop the bacteria from building these defenses. The team started by screening 91 compounds that contain a certain chemical structure which has been seen to prevent other kinds of bacteria from building biofilms.
Of those, a compound called C10 was found to have the desired effect on the TB bacteria – although it didn't kill the bugs itself, C10 prevented them from hiding under a biofilm. In experiments, when the team paired the compound with existing antibiotics like isoniazid, the combo was enough to wipe out the infection.
Better yet, with C10 around far less isoniazid was needed to kill the bacteria, and spontaneous resistance to the drug never developed.
"By combining C10, or something like it, with isoniazid we could enhance the potency of the antibiotic and block the TB bacteria from developing drug resistance," says Christina Stallings, co-senior author of the study. "That means we might be able to shorten the treatment regimen."
Most promising of all, though, is the fact that C10 appears to help reverse drug resistance that bacteria have already developed. The team tested the combination of C10 and isoniazid on TB bacteria that was already resistant to isoniazid, and found that it was able to kill the bugs.
"This was a totally unexpected finding," says Stallings. "We had no idea we would be able to reverse drug resistance. But this could mean that with all those millions of isoniazid-resistant TB cases, if we use something like C10, we could give people the option of using isoniazid again."
As promising as these results are, the team cautions that it isn't ready for use in humans or animals just yet. These experiments were conducted on bacteria in a lab setting, so more work is still needed to check that it's safe in the body.
"We have this great compound, and we've shown that it's possible to prevent and reverse antibiotic resistance," says Stallings. "But now we have to either improve on the compound itself so we can start testing it in animals, or figure out how it prevents biofilm formation so we can develop other drugs that target the pathway. We have a new strategy to treat TB, but it's going to take time before it's a reality."
The research was published in the journal PNAS.
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