Researchers Investigate New Treatments for Tuberculosis

Antibiotic drug therapies are commonly prescribed to treat persons infected with Mycobacterium tuberculosis, the bacterium that can cause active tuberculosis; however, these antibiotics seem to be becoming less effective over time. Cases of drug-resistant M. tuberculosis strains have been identified and are on the rise. The increase of drug-resistant M. tuberculosis strains is a huge concern for remote areas of the globe, which often do not have access to a wide spectrum of drug therapies beyond the first-line antibiotics, isoniazid and rifampin. Multi-drug resistance is also now on the rise in China, where 6% of new tuberculosis cases are multi-drug resistant. In central Asia and Eastern Europe, 20% of new cases are multi-drug resistant and a staggering 50% of previously treated patients are resistant, as well.^1,2

To further illuminate the causes behind these increases in drug resistance, the M. tuberculosis genome has been sequenced and researchers are working to deduce how the genetic diversity present in the M. tuberculosis genome affects drug resistance.³ To combat resistance, new first-line antibiotics and diagnostic protocols are being developed with the ability to rapidly identify the best drug treatment based on the particular strain of M. tuberculosis.⁴

Since the 1920s, the Bacillus Calmette–Guérin (BCG) vaccine has been used worldwide to prevent tuberculosis, despite its limited effectiveness. The BCG vaccine is anywhere from 0% to 80% effective at preventing tuberculosis and tends to be less effective in adults as compared to children.⁵Researchers are now working to develop new vaccine candidates.

Dr. Sarah Fortune, a principal investigator involved in tuberculosis research at Harvard University’s Department of Immunology and Infectious Diseases, is working to understand why tuberculosis remains a global concern. In 2011, Dr. Fortune co-authored a publication aimed at identifying M. tuberculosis antigenic targets.⁶ Using a quantitative proteomics strategy and LTQ-FT mass spectrometry (Thermo Scientiﬁc), the researchers identified the mechanism and specificity of Esx-1 substrate protein C (EspC) immunity. EspC, also known as Rv3615c, is a highly immunodominant Region of Difference 2-dependent antigen secreted by M. tuberculosis. The authors found that EspC represented a strong tuberculosis vaccine candidate as compared with the BCG vaccine.

Although discovery of the EspC protein has gained attention from the media as a promising drug therapy, at this time it is unknown if there are any future plans for drug trials in the pipeline for EspC. However, researchers involved in both proteomics and genomics remain committed to improving tuberculosis diagnostics and developing more effective treatments.

References

1. Fortune, S. (2012) “The Surprising Diversity of Mycobacterium tuberculosis: Change You Can Believe In,” Journal of Infectious Diseases, 206(11) (pp. 1642–4).

2. World Health Organization. (2010) “Multidrug and extensively drug‐resistant TB (M/XDRTB): 2010 global report on surveillance and response,” available at http://www.who.int/tb/publications/2010/978924599191/en/.

3. Gao, S., et al. (2012) “Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients,” Journal of Infectious Disease, 206(11) (pp. 1724–33).

4. Lawn, S.D., et al. (2013) “Advances in tuberculosis diagnostics: The Xpert MTB/RIF assay and future prospects for a point-of-care test,” Lancet Infectious Diseases, 13(4) (pp. 349–61).

5. Venkataswamy, M.M., et al. (2012) “In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG,” Vaccine, 30(6) (pp. 1038–49).

6. Millington, K.A., et al. (2011) “Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection,” Proceedings of the National Academy of Sciences of the United States of America, 108(14) (pp. 5730–5).

Post Author: Emily Humphreys. As a biology undergraduate at the University of Utah, Emily balanced a heavy class schedule while working long hours in a lab studying eye development. Following graduation, she became involved in infectious disease and aging research involving SNPS.

While she enjoyed the thrill of research, Emily has since traded bench work for science journalism.
And has been a regular contributor to Accelerating Science since 2012.