title: A new Mycobacterium tuberculosis smooth colony reduces growth inside human macrophages and represses PDIM Operon gene expression. Does an heterogeneous population exist in intracellular mycobacteria?
abstract: Mycobacterium tuberculosis (MTB) colony morphology was associated to the pathogen's virulence. We isolated a new MTB H37Rv smooth colony, which only appeared following human macrophages (MDM) infection. The new phenotype was Alcohol-Acid resistant, but devoid of a covering capsule and biofilm defective. We ascertained that there were no deletions in the Rv0096-Rv0101 PDIM Operon, but that its expression was repressed as compared to MTB wild type (wt). Its lipid composition displayed lower PDIM components and higher TAG as compared to wt. In MDM it induced the sigma factors sigB, sigI and sigL expression vs. synthetic medium culture, while it repressed other six sigma factors. It also induced, significantly more than wt, mprA, a mycobacterial persistence regulator. It was phagocytosed more than wt by MDM, where it grew significantly less, but persisted therein till 14 days infection. It induced significantly less IFN-γ, IL-12 and IL-27 transcription than wt in infected MDM, while it increased the transcription of inducible NOS. It resided in mature, LAMP-3 positive phagolysosomes, where it never formed cords. This apparently "weaker" colony might represent an adaptive intracellular phenotype, whose infection may be less productive, but probably better equipped for a long lasting persistence in mildly activated host cells.
authors: Institute of Cell Biology and Neurobiology, National Research Council (IBCN_CNR), Via E. Ramarini 32, 00016 Monterotondo Scalo, Rome, Italy.
authors: Daniela
authors: D
authors: Giovannini
authors: Giulia
authors: G
authors: Cappelli
authors: Lina
authors: L
authors: Jiang
authors: Concetta
authors: C
authors: Castilletti
authors: Alessia
authors: A
authors: Colone
authors: Annalucia
authors: A
authors: Serafino
authors: Francesca
authors: F
authors: Wannenes
authors: Luciano
authors: L
authors: Giacò
authors: Gianluca
authors: G
authors: Quintiliani
authors: Maurizio
authors: M
authors: Fraziano
authors: Ridvan
authors: R
authors: Nepravishta
authors: Vittorio
authors: V
authors: Colizzi
authors: Francesca
authors: F
authors: Mariani
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development* / Q000302:isolation & purification / Q000378:metabolism; D009876:Operon; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D018664:Interleukin-12; D007372:Interferons