title: Lipoprotein LpqS deficient M. tuberculosis mutant is attenuated for virulence in vivo and shows protective efficacy better than BCG in guinea pigs.
abstract: Bacterial lipoproteins are a functionally diverse class of membrane anchored proteins. Lipoproteins constitute nearly 2.5% of the Mycobacterium tuberculosis proteome. Inactivation of genes coding for individual lipoproteins results in attenuated phenotype of the mutants. LpqS is a lipoprotein highly conserved among slow growing pathogenic mycobacteria. Our previous study has shown that the lpqS gene deletion mutant of M. tuberculosis (MtbΔlpqS) poorly replicates in THP1-(human acute monocytic leukemia cell line) derived macrophagic cell line. In addition, guinea pigs, when infected with the mutant strain exhibited significantly reduced bacterial burden and pathological damage in the infected tissues in comparison with the parental strain infected group. Subsequently, we evaluated the protective efficacy of the mutant by immunization of guinea pigs through aerosol and subcutaneous routes. We observed that immunization of guinea pigs with MtbΔlpqS offered superior protection in lungs as compared to BCG. In addition, MtbΔlpqS also prevented the haematogenous spread of the disease which was evident from the significantly reduced splenic bacillary load compared to saline vaccinated animals. The gross pathological observations and the histopathological observations well corroborated the bacterial findings. We also observed that aerogenic route of immunization imparts superior protection compared to subcutaneous route of immunization. These findings well establishes the efficacy of M. tuberculosis mutant in imparting protection against pulmonary TB.
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis, Mayor Sathiyamoorthy Road, Chetpet, Chennai 600031, India.
authors.forename: Suba
authors.initials: S
authors.lastname: Sakthi
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis, Mayor Sathiyamoorthy Road, Chetpet, Chennai 600031, India.
authors.forename: Kannan
authors.initials: K
authors.lastname: Palaniyandi
authors.affiliation: National JALMA Institute for Leprosy and Other Mycabacterial Diseases, Tajganj, Agra 282001, India.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Gupta
authors.affiliation: National JALMA Institute for Leprosy and Other Mycabacterial Diseases, Tajganj, Agra 282001, India.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis, Mayor Sathiyamoorthy Road, Chetpet, Chennai 600031, India. Electronic address: sujatha.sujatha36@gmail.com.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics*; D016207:Cytokines / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D006168:Guinea Pigs; D007114:Immunization / Q000379:methods; D008074:Lipoproteins / Q000235:genetics*; D008168:Lung / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D013154:Spleen / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence
chemical_list: D001500:BCG Vaccine; D001426:Bacterial Proteins; D016207:Cytokines; D008074:Lipoproteins; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated
keywords: Gene deletion mutant; Guinea pig model; Live attenuated vaccines; M. tuberculosis; MtbΔlpqS