title: Expression profiling of Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis in acid-nitrosative multi-stress displays defined regulatory networks.
abstract: Several studies regarding the transcriptome of Mycobacterium tuberculosis following the exposure to various in vitro simulated phagosomal stressors, have already tried to elucidate the bacterium behavior during the intracellular infection. An in vitro acid-nitrosative multi-stress was carried out for M. tuberculosis H37Rv and Mycobacterium smegmatis MC(2)155 in order to analyze by DNA-microarray the gene expression changes associated respectively to pathogenic and non-pathogenic mycobacterial species. During acid-nitrosative multi-stress both mycobacteria shift their transcriptome to allow the anaerobic respiratory state and energy pathways characteristic of starvation. M. tuberculosis counteracts the combined acid-nitrosative stress more efficiently than M. smegmatis as also shown by the up-regulation of glbN and hmp genes, that are specifically directed to NO detoxification. Moreover, the down-regulation of some virulence factors involved in phthiocerol dimycocerosates synthesis strengthens the hypothesis that these major virulence determinants may be attenuated by M. tuberculosis in the presence of reactive nitrogen species. In fact, it down-regulates other genes implicated in the synthesis of membrane structural lipids but in contrast to M. smegmatis, M. tuberculosis up-regulates many genes annotated for the synthesis of peptidoglycan. Results suggest a gene regulation of M. tuberculosis which reveals a distinctive expression pattern under stressful environment.
authors.affiliation: Department of Food Science, Division of Food Microbiology, University of Massachusetts, Amherst, MA 01003, USA. Electronic address: andrcossu@yahoo.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossu
authors.forename: Leonardo Antonio
authors.initials: LA
authors.lastname: Sechi
authors.forename: Ennio
authors.initials: E
authors.lastname: Bandino
authors.forename: Stefania
authors.initials: S
authors.lastname: Zanetti
authors.forename: Valentina
authors.initials: V
authors.lastname: Rosu
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D004734:Energy Metabolism / Q000235:genetics*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D008055:Lipids / Q000096:biosynthesis / Q000235:genetics; D020102:Mycobacterium smegmatis / Q000235:genetics* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010457:Peptidoglycan / Q000096:biosynthesis / Q000235:genetics; D012977:Sodium Nitrite / Q000494:pharmacology*; D013312:Stress, Physiological / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics; D054793:Truncated Hemoglobins / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; C102539:GlbN protein, bacteria; D008055:Lipids; D010457:Peptidoglycan; D054793:Truncated Hemoglobins; D037521:Virulence Factors; D009569:Nitric Oxide; C008901:phthiocerol dimycocerosate; D012977:Sodium Nitrite
keywords: Acid-nitrosative multi-stress; DNA-Microarray; Functional genomics; Mycobacterium smegmatis; Mycobacterium tuberculosis; Virulence factors