Lipoprotein LpqS deficient M. tuberculosis mutant is attenuated for virulence in vivo and shows protective efficacy better than BCG in guinea pigs. Issue 6 (3rd February 2016)

• Record Type: Journal Article
• Authors: Sakthi, Suba; Palaniyandi, Kannan; Gupta, Umesh D.; Gupta, Pushpa; Narayanan, Sujatha
• Is Part Of: Vaccine. Volume 34:Issue 6(2016)
• Page Start: 735
• Page End: 743
• Publication Date: 2016-02-03
• Subjects: M. tuberculosis -- MtbΔlpqS -- Gene deletion mutant -- Live attenuated vaccines -- Guinea pig model; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.12.059
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: M. tuberculosis mutant MtbΔlpqS exhibits impaired multiplication in vitro under acidic pH and hypoxic conditions. MtbΔlpqS mutant is attenuated for growth and virulence in vivo in guinea pig model of infection. Gene deletion mutant MtbΔlpqS offers superior protection than BCG in guinea model of tuberculosis infection. Aerogenic route of MtbΔlpqS immunization offers better protection compared to subcutaneous route of immunization 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.