Tuberculosis

Figure 1

Tuberculosis (TB) is a well-known human disease caused by mycobacterium tuberculosis (mtb); mtb is a successful intracellular pathogen that persists within host phagocytes in which they can survive and remain in the dormant stage in macrophages and interfere with the host immune system to avoid elimination by the effector immune cells. TB is considered a major infectious disease even though there have been many advances in treatment and management. Tuberculosis is a topic that I am fascinated in because I will be in the medical field very soon and it is interesting to see medicine making such advances. Tuberculosis can be quickly treated over a period of six months with a multidrug regimen of first line drugs, but this strategy fails to remain effective for various reasons. One of the main reasons is due to patient noncompliance because patients do not have the desire to continue treatment for so long, and eventually become discouraged. There are also problems such as inappropriate drug levels, and drug shortages due to the fact that a majority of the treatment drugs come from third world countries and are not FDA approved. These drugs have also been associated with mild to severe side effects, in turn forcing the treatment to be discontinued due to poor health and immunity of TB patients. Common side effects may include dizziness, muscular twitching, loss of vision or hearing, and acute renal failure. The issue that also circulates is the fact that although the activation of autophagy enhances phagosome-lysosome fusion and regulates mtb growth in host cells, mtb has evolved enough to the point where it overcomes the autophagic process. This study focuses on creating a drug combination that is successful in overcoming the ability of mtb to hide in macrophage by enhancing autophagy, and also does not cause severe host damage. The drug selected in this study for effective TB treatment was pasakbumin A along with anti-TB drug rifampicin. The researchers suggest that pasakbumin A could become more useful for an anti-TB drug or host-directed therapeutic strategy to prevent host cell death and improve host defense mechanisms against mtb infection. 

            

There were multiple experiments to test the hypothesis of whether or not this drug could be as effective as predicted. One experiment conducted was to test whether pasakbumin A had an effect on the induction of different cell death mechanisms as far as autophagy and apoptosis. Autophagy is the natural, regulated mechanism of the cell that disassembles unnecessary or dysfunctional components. It allows for the orderly degradation and recycling of cellular components. In other words, autophagy is a detox process the body undergoes to clean out damaged cells and regenerate new ones (Figure 2). Apoptosis, on the other hand, is a form of cell death in which a programmed sequence of events that leads to the elimination of the entire cell without releasing harmful substances in the surrounding area. Apoptosis plays a critical role in developing and maintaining the health of the body by eliminating old, unnecessary, and unhealthy cells. Results of this experiment showed that it blocked host cell death via apoptosis and treatment of INH (isonicotinylhydrazide, an antibiotic) and pasakbumin A reduced intracellular mtb growth. This suggests that the combination of pasakbumin A and an anti-Tb drug is able to decrease the infection while keeping the cells healthy.  

Figure 2

The results of this study do correspond with the hypothesis that was made. Research showed that pasakbumin A was successful in inhibiting intracellular mtb growth; and also protected the host cells from mtb-induced apoptotic cell death. Pasakbumin A is also a logical TB drug treatment because research showed that activation of autophagy, which is a lysosomal self-degradation process for cellular homeostasis and functions as an innate defense mechanism during mtb infection, induced by pasakbumin A also may aid in its antibacterial effects. To wrap all of this information up, treatment of both the anti-TB drug RMP with pasakbumin A suppressed intracellular mtb growth by promoting autophagy. Understanding how this drug works during mtb infection will open doors to new information about the development of therapeutic anti-TB drugs and future host directed therapeutic strategies that modulate the host immune response against mtb infection. 

Although pasakbumin A seems to be very successful in achieving the goal that was proposed, there are some complications and limitations that may prevent this procedure and regimen from becoming successful. Pasakbumin A is a traditional medicine that comes from a third world country and is used for a variety of conditions which is the main reason why it was investigated. Setbacks may include the fact that the researchers are using a drug that is not approved by the FDA for use in the United States and other researchers may have an issue duplicating this experiment because the researchers had to isolate and purify the drug themselves. The problem with this is the fact that each new batch of medicine will vary. Will western medicine be able to adopt this concept and incorporate it into a new TB drug regimen?

Read more here: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199799

Works Cited:

 “Pasakbumin A Controls the Growth of Mycobacterium Tuberculosis by Enhancing the Autophagy and Production of Antibacterial Mediators in Mouse Macrophages.” PLOS ONE, Public Library of Science, journals.plos.org/plosone/article?id=10.1371/journal.pone.0199799. 

Find image 1 here: https://www.vectorstock.com/royalty-free-vector/treatment-of-tuberculosis-world-tuberculosis-day-vector-20421349
 
Find image 2 here: https://www.ncbi.nlm.nih.gov/books/NBK116074/figure/autophagy_figure1/