Bacteria are often viewed in a negative manner as disease causing agents that are not kind to a human host. Mycobacterium tuberculosis (M. tb) is the epitome of a “bad bug” that can be detrimental to human health. On ASM microTalk, Karl Klose discussed the history of disease, antibiotic treatment, and M. tb pathophysiology with Bill Jacobs from the Albert Einstein College of Medicine. M. tb is the pathogenic bacterium responsible for causing the deadly disease tuberculosis (TB). Even with a vaccine available, TB is the leading cause of death from an infectious agent worldwide, with a staggering 1.5 million deaths from TB in 20181. TB is particularly problematic and deadly in low-income countries due to their healthcare programs not providing adequate coverage to obtain effective antibiotics to treat the disease. Antibiotic treatment of TB is fairly challenging, where patients typically take a combination of antibiotics for an extended period of time.
One of the main reasons that antibiotic treatment of TB is challenging is because M. tb grows at a slow rate. Interestingly, M. tb has a doubling time of 24 hours under the correct conditions, which is much longer than rapidly dividing cells like E. coli that have a doubling time of only 20 minutes2. Since most antibiotics target active processes that occur in dividing cells like cell wall synthesis, slow division is an advantageous mechanism by which M. tb avoids antibiotic killing. An extended period of time will be needed for antibiotics to be effective due to this slow growth, and this is the reason why treatment courses for TB are spanned over several months. An additional explanation for why TB is difficult to treat with antibiotics relates to mycolic acids that are found within M. tb’s cell wall. Mycolic acids contain up to 70-90 carbon atoms, making them extremely hydrophobic3. This hydrophobic outer barrier prevents the uptake of hydrophilic antibiotics, limiting the repertoire of antibiotics that can be used for treatment to small hydrophilic molecules like rifampicin that can pass through the barrier.
The mechanism by which M. tb is able to persist and survive within the host for an extensive period of time is by surviving the host immune response. In addition to conferring protection against antibiotics, a complex cell wall structure helps M. tb avoid the host immune response4. Specifically, during infection, M. tb infects macrophages that normally function to clear pathogens from the body. M. tb is essentially able to hideout and persist within macrophages by preventing intracellular degradation and macrophage apoptosis5. M. tb is capable of surviving in a dormant state until certain conditions within the host arise that result in symptoms and an active infection. This dormant state of M. tb is referred to as a latent state, where the only way that M. tb infection can be detected is through a skin or blood test. M. tb’s ability to persist in a latent state without the host showing symptoms of infection, while also being able to cause a deadly infection in some instances, exemplifies that M. tb is at the forefront of fascinating pathogens.
References
- WORLD HEALTH ORGANIZATION. (2019). Global Tuberculosis Report 2019. S.l.:
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- Lambert, P. (2002). Cellular impermeability and uptake of biocides and antibiotics in Gram positive bacteria and mycobacteria. Journal of Applied Microbiology, 92(s1). doi: 10.1046/j.1365-2672.92.5s1.7.x
- Rohini, K., & Srikumar, P. S. (2013). Insights from the docking and molecular dynamics simulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis. Bioinformation, 9(13), 685–689. doi: 10.6026/97320630009685
- Zhai, W., Wu, F., Zhang, Y., Fu, Y., & Liu, Z. (2019). The Immune Escape Mechanisms of Mycobacterium Tuberculosis. International Journal of Molecular Sciences, 20(340), 1 18. doi: doi:10.3390/ijms20020340
