Breaking down the microbiology world one bite at a time
From TB to Treatment (Part 1): Bedaquiline
PART 1
If you were an avid player of computer games in the 90s, you may recall times spent hunkered down, assuming the role of a 19th-century pioneer traversing the Oregon Trail. Along the way, your settlers faced deadly challenges, including bandits, wild animals, and hunger. One of the most common deaths was due to “consumption,” now known as tuberculosis (TB). Fortunately, TB is an entirely curable and preventable infectious disease caused by the bacterial pathogen Mycobacterium tuberculosis. In high-income countries, TB is largely considered to be eradicated and no longer a cause for concern. However, this is not the case globally.
The Problem: Multi-Drug Resistant TB and the Inaccessibility of Life-Saving Treatments
Prior to the emergence of COVID-19, TB was the number one infectious killer worldwide (read this MicroBites article on how TB escapes our immune system). On average, it continues to result in 1.5 million global deaths annually, most of which are from low- and middle-income countries. Alarmingly, multi-drug resistant (MDR) TB that does not respond to the current standard-of-care treatment is on the rise, infecting an estimated 450,000 people each year. MDR pathogens arise and spread through a myriad of methods. Among the most common and dangerous is the overuse of antibiotics; prolonged treatment simultaneously kills susceptible bacterial pathogens and enriches those resistant to that course of antibiotics. The threat of a global antimicrobial resistance (AMR) crisis is imminent.
Map of the estimated TB incidence rates on the left and map of the percentage of people with MDR-TB on the right, for those with no previous history of TB treatment, from the World Health Organization’s Global TB Report 2023.
The Rise of Bedaquiline as Routine Standard-of-Care Treatment
Thankfully, there is a clinical solution: bedaquiline, an antibiotic manufactured by Johnson & Johnson (J&J) that is highly effective against MDR-TB. Bedaquiline was released in 2012 as the first novel TB drug in 46 years and has quickly become the backbone of MDR-TB treatment regimens.
Frequently, a combination of drugs that alter different molecular targets, termed a drug cocktail, is used. Previously, upward of four different antibiotics were used to treat MDR-TB over the course of eighteen months, and this regimen was riddled with life-threatening adverse effects. In this new cocktail, bedaquiline is combined with two other antibiotics, pretomanid and linezolid, to achieve a shorter and less toxic treatment regimen of only six months. Bedaquiline works by blocking the machinery responsible for producing energy for the bacterial cell, thereby resulting in the death of TB cells and subsequent clearance of the infection.
Disease pathology of TB infections: TB spreads via inhaling droplets that contain the bacterium. These droplets are ingested by immune-related cells, recruiting other immune cells to form a barricade in a circular structure called a granuloma. Continued multiplication of the bacterium enables its spread to other parts of the body through the blood and lymphatic system. Bedaquiline inhibits the cellular machinery that makes energy, called ATP synthase, disrupting the delicate balance of its environment, causing cell death. Figure drawn by Fiona Qu
Despite bedaquiline’s quick success, TB persists as the second leading infectious killer. Communicable diseases are multifaceted issues – part two of this article will focus on just one: patent evergreening.
For More Information:
To read more about the beginnings of MSF’s campaign, click here.
To read the original press release from Stop TB Partnership, click here.
To read MSF’s take on patent evergreening, click here and here.
To check out John Green’s YouTube channel, click here, and for his video to J&J, click here.
Featured image: Generated using AI
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