MHF TOP PICKS FOR December
Every month, we at the Mueller Health Foundation like to showcase interesting news and updates in the field of tuberculosis. Below are our top 3 picks for December:
- Study Finds Weakness in Drug-Resistant Tuberculosis Pathogens
A recent study has uncovered potential weaknesses in drug-resistant strains of Mycobacterium tuberculosis, providing hope for combating the global challenge of tuberculosis. Drug resistance, particularly to the first-line antibiotic isoniazid, is often linked to mutations in the katG gene, which encodes the catalase-peroxidase enzyme KatG. Researchers hypothesized that the disrupted KatG activity in isoniazidresistant strains could create collateral vulnerabilities. Using advanced tools such as whole-genome CRISPR interference (CRISPRi) screens, transcriptomics, and metabolomics, they identified key weaknesses in the physiology of katG-mutant TB strains. The study revealed that while metabolic and transcriptional reprogramming compensates for the loss of KatG, this adaptation generates vulnerabilities in critical processes such as respiration, ribosome biogenesis, and nucleotide and amino acid metabolism. Notably, these vulnerabilities were found to be more pronounced in isoniazid-resistant mutants, making them highly sensitive to targeted inhibition. This finding was validated in clinical isolates, suggesting that these druggable vulnerabilities could pave the way for new treatment strategies. To learn more, you can access the article at: https://www.nature.com/articles/s41467-024-54072-w
- New Mechanism Uncovered Behind Immune Decline after Tuberculosis Treatment
Researchers at Baylor College of Medicine have identified a mechanism responsible for the persistent decline in immune function observed after successful tuberculosis treatment. Their study reveals that severe infections like TB induce lasting epigenetic changes—specifically, increased DNA methylation—that suppress immune responses, elevating the risk of subsequent infections. The team discovered that heightened activity in the tricarboxylic acid (TCA) cycle, a central metabolic pathway, correlates with these epigenetic modifications. By administering everolimus, an inhibitor of TCA cycle activation, alongside standard TB antibiotics, they effectively reduced harmful DNA methylation marks in patients, suggesting a potential strategy to restore immune function post-infection. This approach holds promise not only for TB but also for enhancing immune recovery following other severe infections.
DID YOU KNOW?
In the wake of the devastating 2019 fire at Paris’s Notre-Dame Cathedral, archaeologists recently uncovered an extraordinary find beneath the floors: two lead coffins, also known as sarcophagi.
One of the sarcophagi was identified as belonging to Antoine de la Porte, a prominent canon who passed away in 1710. The second discovery was even more intriguing. It contained the remains of a man in his mid-30s who showed signs of tuberculosis and meningitis—diseases that plagued him during his final years.
Forensic analysis and historical context suggest that these remains could belong to Joachim du Bellay, a celebrated French Renaissance poet known for his poignant and melancholic works. Du Bellay, who died in 1560 at the age of 37, had long been a historical mystery regarding his burial location. This discovery provides a compelling new chapter in understanding his life and death.
This remarkable discovery intertwines art, history, and science, offering a deeper look into the life of one of France’s literary icons while highlighting the health struggles of a bygone era. It’s a poignant reminder of the intersection between culture and the human condition across centuries.
The find is not just a window into 16thcentury burial practices but also a reminder of the enduring toll of tuberculosis, a disease that was rampant during Du Bellay’s time and remains a major global health challenge today.
