Healthcare (Commonwealth Union) – Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It primarily affects the lungs but can also impact other parts of the body, such as the brain, kidneys, and spine. TB has been a significant global health concern for centuries, with its history dating back to ancient times.
A new study reveals that a modified compound derived from bloodroot, a wildflower native to North America, shows strong potential in combating multidrug-resistant tuberculosis (TB) bacteria in laboratory tests.
Published in Microbiology Spectrum, the research offers hope for developing new treatments for TB, which is the second deadliest infectious disease globally after COVID-19, according to the World Health Organization.
Dr. Jim Sun, senior author and assistant professor at the University of British Columbia’s department of microbiology and immunology indicated that there is a critical need to enhance our arsenal of drugs to combat multidrug-resistant TB, either by shortening treatment duration or preventing resistance.
He further stated that the current TB drugs are over 50 years old and unlike other bacterial infections, TB requires a minimum of six months of treatment with a mix of medications, which poses a considerable burden on the body.
In their search for new TB treatments, the researchers focused on sanguinarine, a compound found in the bloodroot plant, known for its antimicrobial and antiseptic qualities.
While natural compounds often serve as strong candidates for developing anti-infective drugs, they are usually more toxic to humans. To address this, the research team modified sanguinarine to boost its effectiveness while lowering toxicity. This resulted in the creation of 35 new derivatives, two of which—BPD9 and BPD6—showed over 90% inhibition of Mycobacterium tuberculosis, the bacterium responsible for TB, even at low doses in lab tests.
According to the team, both compounds proved effective against three highly aggressive TB strains and five strains resistant to multiple existing antibiotics.
In mouse models infected with a weakened strain of TB, BPD9 significantly reduced bacterial levels in the lungs within just eight days.
“We were thrilled to see that the BPD compounds were effective even against multidrug-resistant strains. We look forward to investigating further how they work compared to existing antibiotics,” explained the first author Yichu Liang, who is a UBC and University of Ottawa doctoral student.
The researchers suggest that BPD9 could also be useful in treating dormant tuberculosis (TB). “TB treatment takes six months because the bacteria can ‘hibernate’ in your lungs until reactivated. Most antibiotics work best against actively growing bacteria, but BPD9 seems to be able to stop dormant bacteria from coming back to life,” explained Dr. Sun. Additionally, the BPD compounds specifically target the mycobacteria family, sparing other types of bacteria and thereby protecting the human microbiome.
This specificity extends to non-tuberculous mycobacteria, which are increasingly recognized as important pathogens. Dr. Andréanne Lupien, co-first author and assistant professor in the department of microbiology and immunology at McGill University noted that certain species are notoriously resistant to current antibiotics, and treatment outcomes are often poor, especially for patients with pre-existing lung conditions.
Dr. Lupien further stated that for these difficult-to-treat infections, developing and evaluating new therapeutic options, like BPD9, with a novel mode of action, is crucial.
Although the preclinical findings are encouraging, the researchers stress that there’s still much to do. The next steps involve further reducing the compounds’ toxicity, optimizing their effectiveness, and conducting additional tests on drug-resistant strains of TB-causing bacteria.
The team will also focus on understanding how the BPD compounds work within the bacteria, aiming to improve the potency of any resulting treatments.
