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Autophagy and Biological Therapies: Are they Revolutionary Forces in Tuberculosis Treatment?

Written by Ava Smith, Edited by Han Trieu

Tuberculosis Introduction 

Tuberculosis is a disease that can cause persistent cough, chest pain, and fever.6 Amongst individuals in the United States, it has become highly misunderstood and underestimated. Many Americans don’t know what Tuberculosis is, and the majority of those who do falsely believe that it is an eradicated disease, much like Smallpox.1 However, in 2023, tuberculosis was the leading cause of death from infectious disease worldwide, with total deaths ranging between 1-3 million.1 Every year, 8 million people are diagnosed with tuberculosis,2  with odds of contracting tuberculosis increasing for individuals in the prison system, those with HIV, pregnant women, and healthcare workers.1 In general, individuals are at a higher risk of developing Tuberculosis if they are immunocompromised or if they frequent “high incidence” settings (places with high concentrations of people who have Tuberculosis, like hospitals or prisons). Tuberculosis can only be contracted if tuberculosis bacteria—tubercle bacillus—is present in the lungs, where it can spread to the atmosphere via sneezing or coughing. Further, there are two stages to tuberculosis: the one responsible for the high number of tuberculosis deaths each year is active tuberculosis disease, which is preceded by latent tuberculosis infection (LTBI).1 


Biology of Tuberculosis Infection v. Tuberculosis Disease 

Tuberculosis infection is not contagious, even if it’s found in the lungs. This is because tuberculosis bacteria is present in the body, but it is contained in granulomas, a tissue produced by the immune system to prevent the spread of bacteria.3 Because tubercle bacillus is not free floating in the body, sneezing or coughing won’t spread Tuberculosis bacteria to other people. However, tubercle bacillus is eventually able to bypass granuloma confinement because it is a type of mycobacteria. Mycobacteria have a unique structure that allow them to evade containment attempts by the immune system, including granulomas. Tubercle bacilli eventually break free of granulomas, causing them to dissolve.2 When this occurs, bacteria escapes, spreading and reproducing in the body. This process officially marks the transition from latent Tuberculosis infection to active Tuberculosis disease, as the patient becomes symptomatic and highly contagious. Currently, tuberculosis infection’s progression can be inhibited with the use of medications, but drug-resistant cases of Tuberculosis are seen across patient demographics.1 Further, using tuberculosis medications can produce undesirable side effects, including chronic fatigue, nausea, or, in some cases, irreversible disabilities.1 For these reasons, it is difficult to use drugs designed to treat tuberculosis for long periods of time, and short-term forms of treatment are ideal.1


Autophagy and Tuberculosis 

In the case of Tuberculosis, granuloma formation occurs when autophagy, a process that typically prevents the spread of infectious disease, is inhibited.5 Normally, foreign bacteria taken up by an immune cell, such as macrophages, are sequestered in a specialized double-membrane intracellular vesicle called an autophagosome. This autophagosome then fuses with a lysosome, an organelle packed with acidic enzymes that breaks down these cells and recycles the parts of them that can be reused in cellular processes.4 Tubercle bacillus (and other kinds of mycobacteria) is able to evade autophagy by “hijacking” macrophages.5  Tubercle bacillus is absorbed by macrophages but is not deposited to the lysosome. Instead, tuberculosis bacteria survive and replicate inside macrophages, which form chronic granulomas.5 


Autophagy as Biological Treatment for Tuberculosis 

If there was a way to prevent tubercle bacillus’s hijacking of the immune system, then the traditional means of targeting infectious disease would serve as an effective treatment for Tuberculosis. Currently, research is being done to investigate biological means of treating Tuberculosis that rely on adaptations to the system of autophagy. Specifically, autophagy inducers could strengthen macrophage's ability to consume tubercle bacillus, allowing macrophages to overcome challenges posed by mycobacteria’s unique structure and break them down like any other bacteria. These inducers could be combined with current pharmaceutical treatments for Tuberculosis—isoniazid, rifampicin, ethambutol, and pyrazinamide—to improve treatment efficacy and reduce the amount of prescribed medication needed to treat Tuberculosis.5 If individuals begin using this “hybrid” medication during the infection stage, then they could make a full recovery in a shorter amount of time and experience less undesirable symptoms in the process. This treatment option is especially desirable for drug-resistant cases of tuberculosis.5


Conclusion 

Tuberculosis is an infectious disease that defines the lives of millions of individuals. Tuberculosis is resistant to biological processes like autophagy because its associated bacteria—tubercle bacillus—is a mycobacterium. Knowing this, Tuberculosis could potentially be treated using autophagy inducers. Autophagy inducers are a kind of “enhancer,” and their use would strengthen macrophages’ ability to defend the immune system. Research suggests that, if induced, macrophages are able to break down tubercle bacillus like any other bacteria, preventing it from existing and replicating inside cells. Combining autophagy inducers with existing drugs for treating Tuberculosis has produced preliminary results that support the use of biological therapies for Tuberculosis treatment, especially for those who don’t benefit from the use of existing therapies.

References

  1. Trajman, A., Campbell, J. R., Kunor, T., Ruslami, R., Amanullah, F., Behr, M. A., & Menzies, D. (2025). Tuberculosis. The Lancet, 405(10481), 850–866. https://doi.org/10.1016/s0140-6736(24)02479-6

  2. Bento, C. F., Empadinhas, N., & Mendes, V. (2015). Autophagy in the Fight Against Tuberculosis. DNA and Cell Biology, 34(4), 228–242. https://doi.org/10.1089/dna.2014.2745

  3. CDC. “Clinical Overview of Tuberculosis.” Tuberculosis (TB), Center for Disease Control, 6 Jan. 2025, www.cdc.gov/tb/hcp/clinical-overview/index.html. Accessed 19 Mar. 2026.

  4.  Cleveland Clinic. “Autophagy: Definition, Process, Fasting & Signs.” Cleveland Clinic, 23 Aug. 2022, my.clevelandclinic.org/health/articles/24058-autophagy. Accessed 20 Mar. 2026.

  5. Gina, P, et al. “Manipulation of Autophagy for Host-Directed Tuberculosis Therapy.” African Journal of Thoracic and Critical Care Medicine, vol. 25, no. 2, 31 July 2019, p. 10.7196/AJTCCM.2019.v25i2.014, pmc.ncbi.nlm.nih.gov/articles/PMC8278992/, https://doi.org/10.7196/AJTCCM.2019.v25i2.014. Accessed 20 Mar. 2026.

  6. Centers for Disease Control and Prevention. (2024, May 3). Signs and Symptoms of Tuberculosis. Tuberculosis (TB). https://www.cdc.gov/tb/signs-symptoms/index.html

This post is not a substitute for professional advice. If you believe that you may be experiencing a medical emergency, please contact your primary care physician, or go to the nearest Emergency Room. Results from ongoing research are constantly evolving. This post contains information that was last updated in May 2026.


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