Research May Drive Improved TB Treatments and Drug Resistance Strategies
New Jersey: Researchers at Rutgers New Jersey Medical School have uncovered why the relatively new antibiotic bedaquiline is effective against multidrug-resistant tuberculosis (TB), shedding light on potential new approaches for treatment and drug development.
Key Findings: Vulnerabilities in Drug-Resistant TB Strains
The study found that TB bacteria with deficiencies in the enzyme catalase-peroxidase, encoded by the gene katG, are more vulnerable to bedaquiline. This deficiency, often associated with resistance to the antibiotic isoniazid, increases the bacteria’s susceptibility to DNA damage and reactive oxygen species, weakening it against the newer drug.
Implications for Drug Development and TB Control
This discovery could enable more effective use of bedaquiline by potentially lowering doses or shortening treatment durations. Combining bedaquiline with isoniazid also appeared to reduce the risk of resistance development. Additionally, the study suggests that other antibiotics, such as trimethoprim and sulfamethoxazole, may be repurposed to treat drug-resistant TB.
A Broader Vision: Machine Learning and Synthetic Biology
The Rutgers team is now using machine learning to identify further drug-resistant TB vulnerabilities and exploring synthetic biology to prevent resistance. These methods may lead to personalized medicine approaches for TB, tailoring treatment based on specific bacterial characteristics and enhancing the fight against this deadly disease.
Source:
Rutgers University
Journal reference:
Ofori-Anyinam, B., et al. (2024). Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline. Nature Communications. doi.org/10.1038/s41467-024-53933-8.
