title: Recent developments in genomics, bioinformatics and drug discovery to combat emerging drug-resistant tuberculosis.
abstract: Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB control. The delay in diagnosis of DR-TB leads to its increased transmission, and therefore prevalence. Recent developments in genomics have enabled whole genome sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old liquid culture and directly from uncultured sputa, while new bioinformatics tools facilitate to determine DR mutations rapidly from the resulting sequences. The present drug discovery and development pipeline is filled with candidate drugs which have shown efficacy against DR-TB. Furthermore, some of the FDA-approved drugs are being evaluated for repurposing, and this approach appears promising as several drugs are reported to enhance efficacy of the standard TB drugs, reduce drug tolerance, or modulate the host immune response to control the growth of intracellular M. tuberculosis. Recent developments in genomics and bioinformatics along with new drug discovery collectively have the potential to result in synergistic impact leading to the development of a rapid protocol to determine the drug resistance profile of the infecting strain so as to provide personalized medicine. Hence, in this review, we discuss recent developments in WGS, bioinformatics and drug discovery to perceive how they would transform the management of tuberculosis in a timely manner.
authors.affiliation: National Institute for Research in Tuberculosis (ICMR), Chetpet, Chennai, 600031, India. Electronic address: doctorsoumya@yahoo.com.
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (ICMR), Chetpet, Chennai, 600031, India.
authors.forename: Jagadish Chandrabose
authors.initials: JC
authors.lastname: Sundaramurthi
authors.affiliation: Department of Clinical Research, National Institute for Research in Tuberculosis (ICMR), Chetpet, Chennai, 600031, India.
authors.forename: Alangudi Natarajan
authors.initials: AN
authors.lastname: Palaniappan
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (ICMR), Chetpet, Chennai, 600031, India.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Narayanan
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019295:Computational Biology / Q000379:methods; D055808:Drug Discovery / Q000379:methods; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D056726:Genetic Association Studies; D023281:Genomics / Q000379:methods; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents
keywords: Bioinformatics; Drug discovery; Drug-resistant tuberculosis; Personalized medicine; Whole genome sequencing