Fighting Drug-Resistant TB with a Novel Antibiotic

A study published in the American Society for Microbiology journal Microbiology Spectrum reported on a novel semi-synthetic molecule that produces significant activity against strains of Mycobacterium tuberculosis, including those that are resistant to drugs that can be generated from natural compounds. With the help of this novel substance, researchers may be able to create effective new anti-tuberculosis medications.

The organism that causes tuberculosis (TB), M. tuberculosis, is the primary cause of death from bacterial diseases globally. The antibiotic regimens used to treat tuberculosis (TB) today are outdated, necessitate longer treatment periods, and run the risk of causing drug resistance.

Researchers looked for novel drugs that target M. tuberculosis and may be effective against drug-resistant strains of the disease in the latest study. When searching for new antibiotics, one useful resource in drug discovery is the world of naturally occurring chemicals made by bacteria, fungi, and plants.

A flowering herbaceous plant native to North America is used to extract sanguinarine, a naturally occurring chemical with established antibacterial qualities. Although sanguinarine has been used in both conventional and alternative medicine for animals, its toxicity precludes its use as a medication for people.

Using concepts from medicinal chemistry, the team of researchers redesigning sanguinarine created a more effective antibacterial molecule with less toxicity. The enhanced sanguinarine, known as BPD-9, has been shown in tests on mice and test tubes to eradicate strains of M. tuberculosis that are resistant to every first-line antibiotic used in TB clinics.

Furthermore, BPD-9 demonstrated efficacy against both intracellular and non-replicating (dormant) M. tuberculosis, two major factors that restrict the efficacy of available anti-TB medications.

Additionally, the researchers discovered that BPD-9 was limited to inhibiting pathogenic bacteria belonging to the same genus as M. tuberculosis, potentially protecting the microbiome and other beneficial bacteria from harm caused by conventional antibiotics.

Our findings show a new chemical entity that has unique properties in combating Mycobacterium tuberculosis, which may be harnessed further for clinical translation.”

 Jim Sun, Ph.D., Assistant Professor and Study Corresponding Author, Department of Microbiology and Immunology, The University of British Columbia

Sun said, “Our finding that the new compound is effective against other members of the Mycobacterium genus may also prove to be valuable in the fight against deadly lung infections caused by non-tuberculous mycobacteria, which are notoriously resistant to most antibiotics. It is also enticing to speculate that BPD-9 could be killing Mycobacterium tuberculosis in a way that is different than that of existing anti-TB drugs.”