Lipoprotein LpqS deficient M. tuberculosis mutant is attenuated for virulence in vivo and shows protective efficacy better than BCG in guinea pigs.

Suba, S .; Kannan, P .; Gupta, U.D .; Gupta, P .; Narayanan, S .

Vaccine; 2016; 34; 735-743.

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 (Mtb D lpqS) poorly replicates in THP1-(human acute monocytic leukemiacell line) derived macrophagic cell line. In addition, guinea pigs, when infected with the mutant strainexhibited 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 Mtb D lpqS offered superior protection in lungs as compared to BCG. In addition, Mtb D lpqS 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.

Keywords: M. tuberculosis ; Mtb D lpqS; gene deletion mutant; Live attenuated vaccines; Guinea pig model

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