NDLI: Identification of New Drug Targets and Resistance Mechanisms in Mycobacterium tuberculosis

Content Provider	PubMed Central
Author	Ioerger, Thomas R. O’malley, Theresa Liao, Reiling Guinn, Kristine M. Hickey, Mark J. Mohaideen, Nilofar Murphy, Kenan C. Boshoff, Helena I. M. Mizrahi, Valerie Rubin, Eric J. Sassetti, Christopher M. Barry, Clifton E. Sherman, David R. Parish, Tanya Sacchettini, James C.
Editor	Kremer, Laurent
Copyright Year	2013
Abstract	Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis , especially given the increase of resistance worldwide to first- and second-line drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is based on whole-cell screening, coupled with whole-genome sequencing of resistant mutants and recombineering to confirm. The method yields targets paired with whole-cell active compounds, which can serve as novel scaffolds for drug development, molecular tools for validation, and/or as ligands for co-crystallization. It may also reveal other information about mechanisms of action, such as activation or efflux. Using this method, we identified resistance-linked genes for eight compounds with anti-tubercular activity. Four of the genes have previously been shown to be essential: AspS, aspartyl-tRNA synthetase, Pks13, a polyketide synthase involved in mycolic acid biosynthesis, MmpL3, a membrane transporter, and EccB3, a component of the ESX-3 type VII secretion system. AspS and Pks13 represent novel targets in protein translation and cell-wall biosynthesis. Both MmpL3 and EccB3 are involved in membrane transport. Pks13, AspS, and EccB3 represent novel candidates not targeted by existing TB drugs, and the availability of whole-cell active inhibitors greatly increases their potential for drug discovery.
Related Links	http://dx.doi.org/10.1371/journal.pone.0075245
Starting Page	75245
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	9
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

Combined Species Identification, Genotyping, and Drug Resistance Detection of Mycobacterium tuberculosis Cultures by MLPA on a Bead-Based Array

The Association between Mycobacterium Tuberculosis Genotype and Drug Resistance in Peru

Association between Mycobacterium tuberculosis Complex Phylogenetic Lineage and Acquired Drug Resistance

Acquired Resistance of Mycobacterium tuberculosis to Bedaquiline

Spoligotyping and Drug Resistance Analysis of Mycobacterium tuberculosis Strains from National Survey in China

Drug Resistance Profiles of Mycobacterium tuberculosis Complex and Factors Associated with Drug Resistance in the Northwest and Southwest Regions of Cameroon

Pattern of Drug Resistance and Risk Factors Associated with Development of Drug Resistant Mycobacterium tuberculosis in Pakistan

Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic Associations with Drug Resistance

Identification of New Drug Targets and Resistance Mechanisms in Mycobacterium tuberculosis

Similar Documents

Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

Combined Species Identification, Genotyping, and Drug Resistance Detection of Mycobacterium tuberculosis Cultures by MLPA on a Bead-Based Array

The Association between Mycobacterium Tuberculosis Genotype and Drug Resistance in Peru

Association between Mycobacterium tuberculosis Complex Phylogenetic Lineage and Acquired Drug Resistance

Acquired Resistance of Mycobacterium tuberculosis to Bedaquiline

Spoligotyping and Drug Resistance Analysis of Mycobacterium tuberculosis Strains from National Survey in China

Drug Resistance Profiles of Mycobacterium tuberculosis Complex and Factors Associated with Drug Resistance in the Northwest and Southwest Regions of Cameroon

Pattern of Drug Resistance and Risk Factors Associated with Development of Drug Resistant Mycobacterium tuberculosis in Pakistan

Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic Associations with Drug Resistance

Identification of New Drug Targets and Resistance Mechanisms in Mycobacterium tuberculosis