title: PE_PGRS30 is required for the full virulence of Mycobacterium tuberculosis.
abstract: The role and function of PE_PGRS proteins of Mycobacterium tuberculosis (Mtb) remains elusive. In this study for the first time, Mtb isogenic mutants missing selected PE_PGRSs were used to investigate their role in the pathogenesis of tuberculosis (TB). We demonstrate that the MtbΔPE_PGRS30 mutant was impaired in its ability to colonize lung tissue and to cause tissue damage, specifically during the chronic steps of infection. Inactivation of PE_PGRS30 resulted in an attenuated phenotype in murine and human macrophages due to the inability of the Mtb mutant to inhibit phagosome-lysosome fusion. Using a series of functional deletion mutants of PE_PGRS30 to complement MtbΔPE_PGRS30, we show that the unique C-terminal domain of the protein is not required for the full virulence. Interestingly, when Mycobacterium smegmatis recombinant strain expressing PE_PGRS30 was used to infect macrophages or mice in vivo, we observed enhanced cytotoxicity and cell death, and this effect was dependent upon the PGRS domain of the protein.Taken together these results indicate that PE_PGRS30 is necessary for the full virulence of Mtb and sufficient to induce cell death in host cells by the otherwise non-pathogenic species M. smegmatis, clearly demonstrating that PE_PGRS30 is an Mtb virulence factor.
authors: Institutes of Microbiology Physics, Universita' Cattolica del Sacro Cuore, Rome, Italy.
authors: Raffaella
authors: R
authors: Iantomasi
authors: Michela
authors: M
authors: Sali
authors: Alessandro
authors: A
authors: Cascioferro
authors: Ivana
authors: I
authors: Palucci
authors: Antonella
authors: A
authors: Zumbo
authors: Silvia
authors: S
authors: Soldini
authors: Stefano
authors: S
authors: Rocca
authors: Emanuela
authors: E
authors: Greco
authors: Giuseppe
authors: G
authors: Maulucci
authors: Marco
authors: M
authors: De Spirito
authors: Maurizio
authors: M
authors: Fraziano
authors: Giovanni
authors: G
authors: Fadda
authors: Riccardo
authors: R
authors: Manganelli
authors: Giovanni
authors: G
authors: Delogu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D055786:Gene Knockout Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D010588:Phagosomes / Q000382:microbiology; D017434:Protein Structure, Tertiary; D014397:Tuberculosis, Pulmonary / Q000382:microbiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins