Synthetic Biology in Action: Developing a Drug Against MDR-TB

Abstract

The amalgamation of the research efforts of biologists, chemists and geneticists led by scientists at the Department of Zoology, University of Delhi has resulted in the development of a novel rifamycin derivative; 24-desmethylrifampicin, which is highly effective against multi-drug resistant (MDR) strains of Mycobacterium tuberculosis. The production of rifamycin analogue was facilitated by genetic-synthetic strategies that have opened an interdisciplinary route for the development of more such rifamycin analogues aiming at a better therapeutic potential. The results of this painstaking effort of nearly 25 years of a team of students and scientists led by Professor Rup Lal have been recently published in the Journal of Biological Chemistry (www.jbc.org/content/289/30/21142. long). This strategy can now find applications for developing newer rifamycin analogues that can be harnessed to overcome the problem of MDR, extensively drug resistant (XDR) and totally drug resistant (TDR) M. tuberculosis.

Potential Emergence of Multi-quorum Sensing Inhibitor Resistant (MQSIR) Bacteria

“…The high frequency of evolution of multidrug resistant bacteria has deterred scientific community involved in developing novel antibiotics. So much so that pharmaceutical companies are hesitant to make any financial investments [157][158][159]. It's rightly said, as mentioned before that to counter environmental constraints and natural selection bacterial pathogenicity has to and will evolve over time and inhibition of QS has been gauged as the ticket out of this scramble.…”

Mycobacterium aurum is Unable to Survive Mycobacterium tuberculosis Latency Associated Stress Conditions: Implications as Non-suitable Model Organism

“…TB is the second largest killer around the globe after HIV [18]. Remarkable incidence and prevalence rates of tuberculosis infection can be attributed to the competence of its etiological agent to persist as long-term asymptomatic form and simultaneously escape the host defense mechanisms.…”

Two-Year Follow-up Study of Mycobacterium tuberculosis Antigen-Driven IFN-γ Responses and Macrophage sCD14 Levels After Tuberculosis Contact

“…The World Health Organization (WHO) predicts that by 2020 one billion people will have become newly infected with M.tb, more than 150 million people will have developed active TB, and 36 million will have died as a result of this disease. The emergence of multidrug resistance TB remains a major concern of TB programmes worldwide, which has led to an increased need to understand the mechanisms of drug resistance in M.tb and develop new therapeutic strategies [2,3]. An estimated one-third of the world's population currently suffers from latent TB infection (LTBI) and can be considered a primary source of TB.…”