Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets

by Selleckchem | Apr 30 2023

Mycobacterium tuberculosis (M. tb), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host's immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) M. tb strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB-the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years-reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the M. tb pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in M. tb.

Comments：

Mycobacterium tuberculosis (M. tb) is a highly infectious bacterium that causes tuberculosis (TB), a disease that affects millions of people worldwide. M. tb is a persistent pathogen that can remain dormant in the host's body for many years, only to become active when the immune system becomes compromised. The current treatment protocol for drug-sensitive (DS) M. tb strains is a 6-month regimen involving four different drugs. However, poverty, lack of access to proper treatment, and patient non-compliance have contributed to the emergence of drug-resistant (DR) strains, which require longer treatment durations with more toxic and expensive drugs.

To address the challenges of TB control, several new drugs with novel modes of action have been introduced to the market in recent years. Bedaquiline (BDQ), delamanid (DLM), and pretomanid (PMD) are the first anti-TB drugs to be approved in over 50 years. Despite this progress, the development and approval of new anti-TB drugs remains a significant challenge.

In recent years, several small molecules have been identified as promising anti-TB drug candidates. These compounds target new protein targets in M. tb and have shown efficacy in preclinical and clinical studies. These novel drugs may offer alternative treatment options for TB patients and help to address the challenges of drug-resistant strains.

In summary, TB remains a significant global health concern, and the development of new anti-TB drugs is crucial for effective disease control. While progress has been made, there is still much work to be done to combat this persistent and deadly disease.