Investigating Methods for Fighting Tuberculosis

Despite the different current treatments and detection of tuberculosis, the disease remains a major concern in the health sector, needing more research to fully understand the biological mechanisms underlying the causes, treatment and prevention of TB. Antibiotic resistance in bacterial infections such as these are associated with high mortality rates and heightened costs of treatment often over a long period of time. Infection causing bacteria are equipped with diverse strategies of becoming resistant, consequently, subverting host mechanisms to create disease. It is known that Mtb is associated with prolonged durations of tuberculosis therapy, hence, both Zheng et al. and Mehra et al.’s articles were aimed at investigating the biomechanisms associated with persistence-associated physiologies of Mtb and discovery of new chemical compounds that inhibit expression of DosRST regulon genes, however, they took different approaches in their methods to test out this theory.

Whilst Zheng et al.’s article was based on in vitro studies of these mechanisms with tests limited to macrophages, their results reflected the rational previously discussed. They used the high-throughput screening (HTS) which is very effective and reliable for identification of active compounds, genes or antibodies that modulate specific biochemical pathways. This approach poses the possibility of second order interference between the compounds of interest. However, the chances of this occurring is very low as the targets were tested out in two compound collections. The results were soundly presented with multiple experiment analysis methods to corroborate and emphasize findings. On the contrary, in vitro studies usually produce results relevant to cells isolated from their microsystems, thus, the gap bridging the performance of DosRST in the presence of artemisinin in humans is still yet to be addressed. Furthermore, it is difficult to simulate the cell-to-cell interactions and long-term exposure effects of artemisinin in the body, which makes the results somewhat substandard. Mehra et al.’s approach manipulated the role of dos in modulating immune-responses against Mtb.

They found a high degree of statistical significance in areas of T-cell activation, lymphocyte activation, leukocyte activation, hemopoiesis, T-cell differentiation and T-cell selection involved in the innate clearance of infection and initiation of immune responses. This was not only limited to the microbiologic and pathological features but also in the transcriptional profiles associated with Mtb. The transcriptomic outcomes were supported by reverse-transcriptase PCR for a subset of genes and were highly concordant in the mutant dosR strain. The clinical correlates were adequately accompanied by p-values, showing whether the effects observed were actually attributed to the inhibition of the different Mtb causing strains which is realistically vital for tracking the contribution of each variant of Mtb in drug development and treatment of TB in humans although statistical significance does not account for evaluation of confounding variables, which was not discussed in the article. Implications of these discoveries are wide ranging: with the ability to revolutionise the delivery of treatment to TB patients and develop stronger vaccines, drugs and therapies which would effectively target the disease-causing cells without interfering with the gut microbiome. Overall, whilst taking different routes, both authors similarly, found a way to target Mtb, the challenge is to now increase efficiency and accuracy of these methods.

While the first method may be thoroughly tested and computed, it is impractical in a realistic setting. The second method incorporates mechanisms similar to those experienced by TB patients however, the data is not well presented thus not well understood. There still remains gaps in the knowledge of the biochemical pathways of Mtb. Further topics of research would be recommended in areas of effects of artemisinin and it’s long term effects on human patients whilst also investigating more target points such as blockage of antigen specific antibodies associated with proliferation of Mtb.