Tuberculosis (TB) is an ancient disease that has plagued humans for centuries. It’s caused by a stubborn bacterium called Mycobacterium tuberculosis (Mtb), which attacks the lungs and can be deadly if not treated. While we’ve had antibiotics for TB for quite some time, the problem we’re facing now is that TB bacteria are becoming resistant to many of these drugs. Multidrug-resistant tuberculosis (MDR-TB) is on the rise, and that’s a serious threat to global health.
In an exciting new study, researchers have discovered promising compounds that could offer a new way to tackle this tough disease. They have created and tested two new chemicals—BPD-6 and BPD-9—derived from a natural substance called sanguinarine. Their findings could pave the way for much-needed advancements in TB treatment, particularly against strains that no longer respond to traditional antibiotics.
One of the key challenges with TB treatment today is that it takes a long time. People need to be on antibiotics for at least six months, sometimes longer, and often they’re taking a combination of drugs. This not only makes it harder for patients to stick to their treatment plans, but it also gives the bacteria more chances to evolve and resist the drugs. As lead researcher Yi Chu Liang explains, “The development of drug resistance in TB is a global problem. We need new drugs that work faster and more effectively, especially against resistant strains.”
Liang’s team set out to address this challenge by focusing on natural compounds, which have historically been a great source of medical breakthroughs. For instance, the widely used TB drug rifampicin was originally derived from a natural compound. Sanguinarine, the starting point for their research, has been used in traditional medicine for its antibacterial properties, but until now, no one had explored its potential against TB.
By tweaking the structure of sanguinarine, the team created 35 new compounds and tested them against TB bacteria. Two of these compounds, BPD-6 and BPD-9, stood out for their powerful ability to stop the bacteria in its tracks. What makes these compounds special is their precision—they specifically target Mycobacterium species, which include the bacteria responsible for TB, while leaving other, non-harmful bacteria alone. This is an important benefit because it reduces the chances of disrupting the body’s healthy microbiome, which often happens when broad-spectrum antibiotics are used.
Another promising aspect of BPD-6 and BPD-9 is that they can effectively fight not only the bacteria in its active form but also in their dormant state. Dormant TB bacteria are tricky because they don’t actively replicate, making them less susceptible to many antibiotics. This is one reason TB treatment takes so long; the bacteria hide out, waiting for a chance to become active again. Liang’s research, however, shows that these new compounds are effective even against these sleeping bacteria. “This gives us hope that we might one day shorten the length of TB treatment, making it easier for patients to complete their course of therapy,” says Liang.
But the discoveries don’t stop there. The team tested BPD-9 in mice infected with a type of TB-like bacteria, and the results were encouraging. After just eight days of treatment, the bacterial burden in the mice’s lungs was significantly reduced. This indicates that BPD-9 could potentially work in human patients too, although more testing is needed. The next step would be clinical trials to confirm the safety and effectiveness of these compounds in humans.
What about drug resistance?
Given the ongoing battle with resistant TB strains, it’s crucial to know if these new compounds will fall into the same trap. While some resistance was observed, it was linked to the activation of an efflux pump—a mechanism that bacteria use to flush out harmful substances. Still, these early findings are a sign that the compounds are less likely to be resisted by TB bacteria compared to existing drugs. Liang and his team believe further research could help modify the compounds to overcome this resistance mechanism entirely.
One of the most exciting implications of this research is the potential for combination therapies. TB is rarely treated with a single drug; instead, patients take multiple drugs to hit the bacteria from different angles. In lab tests, when BPD-6 and BPD-9 were combined with rifampicin, one of the standard TB drugs, the results were even better. The combination enhanced the ability to kill the bacteria, which suggests that these new compounds could be used alongside existing drugs to improve treatment outcomes.
Looking ahead, this research opens up new possibilities for future TB treatments. While it’s still early days, and much more testing is required, there’s hope that these compounds could eventually become part of the standard TB treatment regimen. This is particularly important for countries where TB and drug-resistant TB are most prevalent, and where access to effective treatments can be a matter of life and death.
As we face the ongoing global challenge of TB, it’s discoveries like these that remind us of the power of scientific innovation. Liang and his team are cautiously optimistic, recognizing that while there’s still a long way to go, they’ve made a significant step forward. “It’s a tough battle,” says Liang, “but we believe these compounds have the potential to make a real difference in the fight against TB.”
In the near future, we might be looking at a new generation of TB treatments that work faster, more efficiently, and with fewer side effects. For the millions of people affected by TB every year, that day can’t come soon enough.
For more, visit: https://doi.org/10.1128/spectrum.01246-24
