title: Genome-wide expression profiling of the response to linezolid in Mycobacterium tuberculosis.
abstract: Tuberculosis (TB) is still one of the most common causes of death in the world. The emergence of multidrug-resistant and extensively drug-resistant (XDR-TB) Mycobacterium tuberculosis (M. tuberculosis) strains has increased the importance of searching for alternative targets to develop new antimycobacterial drugs. Linezolid, the first of oxazolidinones, is active in vitro against M. tuberculosis, but the response mechanisms of M. tuberculosis to linezolid are still poorly understood. To reveal the possible mechanism of action of linezolid against M. tuberculosis, commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes triggered by treatment with subinhibitory concentrations of linezolid. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. A total of 729 genes were found to be differentially regulated by linezolid. Among these, 318 genes were upregulated, and 411 genes were downregulated. A number of important genes were significantly regulated that are involved in various pathways, such as protein synthesis, sulfite metabolism, and genes involved in the cell envelope and virulence. This genome-wide transcriptomics approach produced the first insights into the response of M. tuberculosis to a linezolid challenge.
authors.affiliation: Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, People's Republic of China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Liang
authors.forename: Xudong
authors.initials: X
authors.lastname: Tang
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Zhang
authors.forename: Aizhen
authors.initials: A
authors.lastname: Guo
authors.forename: Xiuping
authors.initials: X
authors.lastname: Wu
authors.forename: Xuelin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Guan
authors.forename: Lihui
authors.initials: L
authors.lastname: Liu
authors.forename: Fengge
authors.initials: F
authors.lastname: Shen
authors.forename: Mingxun
authors.initials: M
authors.lastname: Xing
authors.forename: Liqiang
authors.initials: L
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D000069349:Linezolid; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D023303:Oxazolidinones / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid