In recent news, researchers from Bengaluru have unveiled a significant discovery regarding the behavior of Tuberculosis (TB) bacteria and its capacity to resist TB drugs. This groundbreaking research highlights the mechanism that the bacteria deploy to become increasingly drug-tolerant.
Understanding the Mechanism
The cornerstone of this mechanism lies in the role of Macrophages, a type of white blood cell. When these cells are infected with pathogens such as bacteria or viruses, they reduce the body’s pH range, making it acidic in the process. Interestingly, the researchers observed that rather than inhibiting the TB bacteria, the mildly acidic pH actually enabled a portion of the bacteria to multiply further and develop drug tolerance.
When Anti-TB drugs instigate oxidative stress to eliminate bacteria within macrophages, the drug-resistant bacteria exhibit an impressive capability to counteract this oxidative stress. The bacteria leverage the acidic pH of macrophages as a signal to augment its resistance towards oxidative stress. Additionally, the bacteria induce efflux pumps that push out antibiotics, effectively reducing antibiotic efficacy.
| Fact | Detail |
|---|---|
| Acidity Level and Drug Tolerance | The more acidic the macrophages (pH 5.8), the more drug-tolerant bacteria were found. Lesser acidity (pH 6.6) had more drug-sensitive bacteria. |
| Treatment Duration | The identified mechanism prolongs TB treatment to six-nine months due to the presence of drug-tolerant bacteria. |
| Common Notion | Contrary to popular belief, not only non-replicating or slowly metabolising TB bacteria can become drug tolerant. |
The Solution Proposed by Researchers
To counter this increasingly challenging scenario, the researchers suggested using a combination of the anti-malaria drug chloroquine and the TB drug isoniazid in mice and guinea pigs. Chloroquine was able to neutralize the pH within the macrophages, preventing the TB bacteria from inducing their defense mechanism against oxidative stress. Consequently, no drug-tolerant TB bacteria emerged.
Results of the Proposed Solution
The application of the neutralizing agent allowed the isoniazid drug to completely eradicate TB from the test animals. The two-month treatment sterilized mouse lungs and facilitated a near-total eradication from the lungs of guinea pigs. Importantly, this drug combination also significantly reduced the chances of TB relapse.
About Tuberculosis (TB)
Tuberculosis is an illness caused by a bacterium known as Mycobacterium tuberculosis that primarily affects the lungs. It is highly transmissible and can be spread from person to person through the air when an infected individual coughs, sneezes, or spits. Symptoms include cough with occasional blood, chest pains, weakness, weight loss, fever, and night sweats.
Despite being highly infectious, TB is a treatable and curable disease. A standard 6-month treatment course comprises 4 antimicrobial drugs provided with information, supervision, and support to the patient by a qualified health worker or trained volunteer.
However, due to prolonged usage, strains resistant to one or more of these medicines have been found globally. These resistant strains result in Multidrug-resistant tuberculosis (MDR-TB) and Extensively drug-resistant TB (XDR-TB). MDR-TB does not respond to isoniazid and rifampicin, the two most potent first-line Anti-TB drugs but can be treated using second-line drugs. XDR-TB, a harsher form of MDR-TB, does not respond to the most effective second-line Anti-TB drugs, often leaving patients with limited treatment options.
