Researchers Have Recently Found a Way to Eradicate the Most Lethal Infectious Disease on Earth

A groundbreaking discovery has revealed a potential method to eradicate tuberculosis, the deadly infectious disease caused by the Mycobacterium tuberculosis bacteria. Scientists have identified a critical system within the bacteria, known as PrrAB, that controls its respiratory function. When researchers disabled PrrAB, the bacteria ceased to survive. Furthermore, an experimental drug, DAT-48, showed even greater effectiveness when combined with PrrAB inhibition.

Although tuberculosis (TB) has been largely overshadowed by COVID-19 in recent years, it remains one of the worlds most deadly diseases. TB, which dates back over 9,000 years, ravaged Europe during the 18th and 19th centuries, and continues to be a global health threat. Despite available treatments, TB has remained prevalent in many regions, particularly in parts of Asia and Africa, and has made a surprising resurgence in countries like the United States, where outbreaks have been reported in California, Kansas, Maine, North Carolina, and New York. The pandemic exacerbated the problem, as lockdowns and fear of contracting COVID-19 kept many people from seeking medical care.

Recent research has revealed that the bacterium Mycobacterium tuberculosis has a genetic vulnerabilitysomething scientists are now eager to exploit. Shelley Haydel, an infectious disease expert at Arizona State University, and her team discovered that the bacterium relies heavily on a molecular system called PrrAB, which functions as the microbes vital mechanism for survival. If this system is disrupted, the bacteria cannot survive.

Using CRISPR interference (CRISPRi) to inhibit PrrAB, the research team was able to kill the bacteria. "The PrrAB two-component system (TCS) is essential for the survival of Mycobacterium tuberculosis, making it an exciting potential target for therapeutic intervention," said Haydel, in a study published in the American Chemical Society: Infectious Diseases journal.

While not all types of mycobacteria were affected by the removal of PrrAB, the technique proved lethal to tuberculosis bacteria in laboratory settings. PrrAB is responsible for regulating the genes required for respiration and oxidative phosphorylation, a process that generates the energy molecule ATP. When PrrAB was repressed, bacterial numbers in the culture dropped by nearly a factor of 100, which is a striking result given the bacteria's role in respiratory infection.

In addition to CRISPRi, the experimental drug Diarylthiazole-48 (DAT-48) was found to be highly effective against the bacteria. DAT-48 works by inhibiting PrrAB, and when combined with CRISPRi, the drug was even more potent. The study found that this combination resulted in an enhanced killing of the bacteria. Even when used alone, DAT-48 showed improved effectiveness when paired with other TB drugs, such as bedaquiline or telacebec, suggesting that the drugs potency is connected to PrrAB's role in bacterial respiration.

"DAT-48, an experimental compound, targets the PrrAB-regulated pathway, demonstrating strong anti-tuberculosis activity and synergy with other respiratory inhibitors," Haydel explained. "These findings underscore the importance of PrrAB as a central control mechanism and confirm DAT-48s potential as a leading candidate for targeted treatments against mycobacterial infections."

While these therapies have not yet been tested in humans, the results in laboratory models suggest that tuberculosis could potentially be eradicated, much like smallpox. If successful in vivo, this could represent a major breakthrough in the fight against one of the world's most persistent and dangerous diseases.

Author: Sophia Brooks