title: The use of microarray analysis to determine the gene expression profiles of Mycobacterium tuberculosis in response to anti-bacterial compounds.
abstract: The response of Mycobacterium tuberculosis to six anti-microbial agents was determined by microarray analysis in an attempt to define mechanisms of innate resistance in M. tuberculosis. The gene expression profiles of M. tuberculosis after treatment at the minimal inhibitory concentration (MIC) for 4 h with isoniazid, isoxyl, tetrahydrolipstatin, SRI#221, SR1#967 and SR1#9190 were compared to untreated M. tuberculosis. A common response to drug exposure was defined, and this expression profile overlapped with a number of other mycobacterial stress responses recently identified by microarray analysis. Compound-specific responses were also distinguished including a number of putative transcriptional regulators and translocation-related genes. These genes may contribute to the intrinsic resistance of M. tuberculosis to anti-microbial compounds. Further investigation into these mechanisms may elucidate novel pathways contributing to mycobacterial drug resistance and influence anti-mycobacterial drug development strategies.
authors.affiliation: Department of Cellular and Molecular Medicine, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE, UK. swaddell@sghms.ac.uk
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Waddell
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stabler
authors.forename: Ken
authors.initials: K
authors.lastname: Laing
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reynolds
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005798:Genes, Bacterial; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial