The rise of antibiotic-resistant strains of tuberculosis means that a new type of tuberculosis treatment is desperately needed. A new type of drug that helps the body fight off tuberculosis shows promise in scientific studies.
Tuberculosis is a bacterial disease that is one of the top 10 causes of death worldwide. Fortunately, it can usually be cured by antibiotic treatment. However, the spread of antibiotic-resistant strains of the bacteria that causes tuberculosis, Mycobacterium tuberculosis, means that many new cases cannot be treated with the most commonly used drugs for tuberculosis treatment. These patients instead have to endure more than a year of treatment with more expensive and toxic drugs. There are even patients whose tuberculosis cannot be treated at all.
Antibiotic treatment leads to antibiotic-resistant bacteria
Most bacteria in nature are not resistant to antibiotics. This is because the extra work of synthesizing the proteins required for antibiotic resistance would slow down bacterial growth and reproduction. However, tuberculosis patients must be treated with antibiotics for several months. During this time, the antibiotics will slowly kill off the regular bacteria, allowing any antibiotic-resistant bacteria in the patient to flourish. A single M. tuberculosis bacterium that mutates to become drug-resistant could then reproduce and eventually become the dominant tuberculosis strain within a patient. At this point, antibiotics will no longer be helpful.
New tuberculosis treatment could slow the rate of infection without killing bacteria
A tuberculosis infection begins with M. tuberculosis penetrating and infecting cells of the immune system. The bacteria grow within the immune cells, releasing various proteins that inhibit the ability of the immune cell to kill the invading bacteria. Drugs that limit the ability of M. tuberculosis to infect immune cells and survive within them may speed up tuberculosis treatment. Quicker treatment should slow the spread of antibiotic resistance in tuberculosis. In a recent study, researchers in the UK and the US have tested a new drug of this type. They published their results in the Journal of Medicinal Chemistry.
The researchers focused on a protein called MptpB. M. tuberculosis uses this protein to help it fight off the body’s immune response. They tested a number of chemicals which could prevent MptpB from working and identified one compound which was particularly effective. The new drug limited the ability of M. tuberculosis to infect immune cells grown in Petri dishes. It did this without actually killing the tuberculosis bacteria outside the immune cells. This means that it shouldn’t encourage further antibiotic resistance. It also helped antibiotics to clear the bacteria from immune cells, suggesting that it would work as a combination therapy with antibiotics.
They then gave the new drug to guinea pigs that had been infected with M. tuberculosis. The drug was not as effective as antibiotics, but it still significantly decreased the severity of the infection.
Can this new tuberculosis treatment fight antibiotic-resistant tuberculosis?
Infecting guinea pigs with antibiotic-resistant strains of M. Tuberculosis could risk the infection of laboratory workers. Instead, the researchers tested the drug on immune cells that they grew in Petri dishes. They found that the new drug limited the ability of antibiotic-resistant M. tuberculosis to infect immune cells.
The new drug still needs to be tested in clinical trials
There is a long road from experiments in guinea pigs to showing that the drug is actually effective in human tuberculosis patients. First, the drug needs further optimization to make it still more efficient. Then it needs to be tested to ensure that it is safe to administer to humans. Finally, it will be tested on actual tuberculosis patients. This could be several years away.
Despite the challenges ahead, the researchers are very optimistic that drugs such as this could help solve the problem of antibiotic-resistant tuberculosis. The same approach could potentially be used to treat other dangerous infections, such as C. difficile.
Written by Bryan Hughes, PhD
- Vickers, C. F., Silva, A. P. G., Chakraborty, A., Fernandez, P., Kurepina, N., Saville, C., Naranjo, Y., Pons, M., Schnettger, L. S., Gutierrez, M. G., Park, S., Kreiswith, B. N., Perlin, D. S., Thomas, E. J., Cavet, J. S. & Tabernero, L. Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo. Journal of Medicinal Chemistry61, 8337-8352 (2018).
- Tuberculosis Fact Sheet. World Health Organization (2018). http://www.who.int/en/news-room/fact-sheets/detail/tuberculosis. Accessed October 2018.
- The University of Manchester. Scientists develop new drug treatment for TB. https://www.manchester.ac.uk/discover/news/scientists-develop-new-drug-treatment-for-tb/. Accessed October 2018.