title: Increased virulence of Mycobacterium tuberculosis H37Rv overexpressing LipY in a murine model.
abstract: We have investigated the role of Rv3097c-encoded lipase (LipY) on the virulence of Mycobacterium tuberculosis. It has been shown that the overexpression of LipY in strain H37Rv induced increase in virulence of recombinant H37Rv::LipY strain. Compared to H37Rv, infection with H37Rv::LipY caused enhanced mortality, weight loss, bacterial load in lungs, splenomegaly, worsening lung morphology and pathology. Mice immunized with recombinant LipY antigen were protected against challenge with H37Rv::LipY, which correlated with enhanced survival of challenged mice and striking decrease in pathological features observed in unimmunized mice. To probe the cause of increase in virulence of H37Rv::LipY, the immune status of the host infected with H37Rv and H37Rv::LipY was compared. It was found that overexpression of LipY compromised immune responses resulting in attenuation of Th1 and Th17 responses, significant increase in IL-10, decrease in number of macrophages and T cells, and increase in numbers of Treg, and DCs in the lungs whereas in mice immunized with LipY an increased pool of T cells and DCs was observed. This led us to conclude that the increase in the virulence of H37Rv::LipY was due to downregulation of the host's protective immunity and the Rv3097c encoded LipY lipase is a virulence factor of M. tuberculosis.
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Lucknow, India. Electronic address: vipulsingh05@gmail.com.
authors.forename: Vipul K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Lucknow, India. Electronic address: Mrigank_Srivastava@cdri.res.in.
authors.forename: Mrigank
authors.initials: M
authors.lastname: Srivastava
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Arunava
authors.initials: A
authors.lastname: Dasgupta
authors.affiliation: Department of Biotechnology, V.B.S Purvanchal University, Jaunpur, India.
authors.forename: Mohan P
authors.initials: MP
authors.lastname: Singh
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Microbiology Division, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Brahm S
authors.initials: BS
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006867:Hydrolases / Q000378:metabolism*; D007111:Immunity, Cellular; D053208:Kaplan-Meier Estimate; D008049:Lipase / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology*; D014611:Vaccination / Q000379:methods; D014774:Virulence; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D011994:Recombinant Proteins; D037521:Virulence Factors; D006867:Hydrolases; D002265:Carboxylic Ester Hydrolases; C000594149:LipY protein, Mycobacterium tuberculosis; D008049:Lipase; C527647:HsaD protein, Mycobacterium tuberculosis
keywords: Immunization; LipY; Mycobacteriun tuberculosis; Overexpression; Protection; Rv3097c; Virulence