Universität zu Köln

Lechartier, Benoit, Rybniker, Jan, Zumla, Alimuddin and Cole, Stewart T. (2014). Tuberculosis drug discovery in the post-post-genomic era. EMBO Mol. Med., 6 (2). S. 158 - 169. HOBOKEN: WILEY. ISSN 1757-4684

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Abstract

The expectation that genomics would result in new therapeutic interventions for infectious diseases remains unfulfilled. In the post-genomic era, the decade immediately following the availability of the genome sequence of Mycobacterium tuberculosis, tuberculosis (TB) drug discovery relied heavily on the target-based approach but this proved unsuccessful leading to a return to whole cell screening. Genomics underpinned screening by providing knowledge and many enabling technologies, most importantly whole genome resequencing to find resistance mutations and targets, and this resulted in a selection of leads and new TB drug candidates that are reviewed here. Unexpectedly, many new targets were found to be promiscuous' as they were inhibited by a variety of different compounds. In the post-post-genomics era, more advanced technologies have been implemented and these include high-content screening, screening for inhibitors of latency, the use of conditional knock-down mutants for validated targets and siRNA screens. In addition, immunomodulation and pharmacological manipulation of host functions are being explored in an attempt to widen our therapeutic options.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lechartier, Benoit UNSPECIFIED UNSPECIFIED UNSPECIFIED Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Zumla, Alimuddin UNSPECIFIED UNSPECIFIED UNSPECIFIED Cole, Stewart T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-447007
DOI:	10.1002/emmm.201201772
Journal or Publication Title:	EMBO Mol. Med.
Volume:	6
Number:	2
Page Range:	S. 158 - 169
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1757-4684
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MYCOBACTERIUM-TUBERCULOSIS; SMALL-MOLECULE; ATP SYNTHASE; INHIBITORS; IDENTIFICATION; RESISTANCE; MECHANISMS; CANDIDATE; RESPONSES; NETWORK Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44700