title: MspA-Mycobacterium tuberculosis-transformant with reduced virulence: the "unbirthday paradigm".
abstract: Expressing mspA porin gene from Mycobacterium smegmatis in Mycobacterium tuberculosis attenuated this pathogen. Intracellular growth of the transformants into free-living amoeba and murine and human macrophages decreased. Furthermore, transformants decreased the microbicidal program of human monocyte-derived macrophages. BALB/c mice inoculated with transformants exhibited higher weights, lower histological lesions and lower M. tuberculosis inoculum in the liver, spleen and lungs than control mice challenged with wild-type M. tuberculosis. Preliminary evaluation indicated that mice inoculated with this transformant showed higher weights and lower numbers of lung nodules and tissular mycobacteria than control mice when challenged with wild-type M. tuberculosis. Similar to the paradoxical "unbirthday" gift coined by Lewis Carroll in Alice's Adventures in Wonderland, adding mspA gene reduced the virulence of M. tuberculosis and yielded a protective effect. Lost of non-virulence genes is a mechanism for virulence in mycobacteria. Engineering non-virulence genes in M. tuberculosis may yield strains with decreased virulence and increased immunogenicity.
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: otmanelamrabet@gmail.com.
authors.forename: Otmane
authors.initials: O
authors.lastname: Lamrabet
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: eric.ghigo@univ-amu.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Ghigo
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: jean-louis.mege@univ-amu.fr.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mège
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: hubert.lepidi@univ-amu.fr.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: claude.nappez@univ-amu.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Nappez
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: didier.raoult@gmail.com.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Aix Marseille Université, URMITE, UM63, CNRS UMR7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: michel.drancourt@univ-amu.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Drancourt
mesh_terms: D000656:Amoeba / Q000382:microbiology; D000818:Animals; D058491:Bacterial Load; D001835:Body Weight; D004195:Disease Models, Animal; D006651:Histocytochemistry; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000382:microbiology; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development*; D018272:Porins / Q000235:genetics*; D014169:Transformation, Bacterial; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology; D014774:Virulence
chemical_list: D018272:Porins; C121838:mspA protein, Mycobacterium smegmatis
keywords: MspA; Mycobacterium smegmatis; Mycobacterium tuberculosis; Porin; Vaccine; Virulence