title: Mycobacterium tuberculosis requires the ECF sigma factor SigE to arrest phagosome maturation.
abstract: SigE represents one of the best characterized alternative sigma factors of Mycobacterium tuberculosis, playing a major role in the response to several environmental stresses and essential for growth in macrophages and virulence. In previous work we demonstrated that a mutant of M. tuberculosis in which the sigE gene was disrupted by a cassette conferring hygromycin resistance is a promising vaccine candidate conferring better protection than Mycobacterium bovis BCG in a mouse model of infection. In this work we describe the construction of a new unmarked mutant in which the entire sigE gene was disrupted in order to fulfill the requirements of the Geneva consensus to enter clinical trials. After showing that the phenotype of this mutant is superimposable to that of the previous one, we further characterized the role of SigE in the M tuberculosis intracellular behavior showing that it is dispensable for replication in human pneumocytes, while it is essential for the arrest of phagosome maturation in THP-1-derived macrophages.
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Casonato
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Provvedi
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dainese
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Manganelli
mesh_terms: D056809:Alveolar Epithelial Cells / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D009569:Nitric Oxide / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D010641:Phenotype; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012808:Sigma Factor; C111259:sigE protein, Bacteria; D009569:Nitric Oxide