Dataset Information

An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs.

ABSTRACT: Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (Mtb?mms) harboring disruption in three genes, namely mptpA, mptpB and sapM Though vaccination with Mtb?mms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with Mtb?mms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by Mtb?mms in spleen of guinea pigs and controls dissemination of the challenge strain, Mtb?mms was genetically modified by disrupting bioA gene to generate Mtb?mmsb strain. Further, in vivo attenuation of Mtb?mmsb was evaluated and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. Mtb?mmsb mutant strain was highly attenuated for growth and virulence in guinea pigs. Vaccination with Mtb?mmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12?weeks post-infection in lungs and spleen of infected animals. However, the protection imparted by Mtb?mmsb was significantly less in comparison to BCG immunized animals. This study indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis for generating protection against tuberculosis.

SUBMITTER: Bahal RK

PROVIDER: S-EPMC5829500 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs.

Bahal Ritika Kar RK Mathur Shubhita S Chauhan Priyanka P Tyagi Anil K AK

Biology open 20180105 1

Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (MtbΔmms) harboring disruption in three genes, namely mptpA, mptpB and sapM Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleen ...[more]

PMID: 29242198

Similar Datasets

Project description:BackgroundThe failure of Mycobacterium bovis Bacille Calmette-Guérin to impart satisfactory protection against adult pulmonary tuberculosis has necessitated the development of more effective TB vaccines. The assumption that the vaccine strain should be antigenically as similar as possible to the disease causing pathogen has led to the evaluation of M.tuberculosis mutants as candidate tuberculosis vaccines.Methods/principal findingsIn this study, we have generated a mutant of M.tuberculosis (Mtb∆mms) by disrupting 3 virulence genes encoding a mycobacterial secretory acid phosphatase (sapM) and two phosphotyrosine protein phosphatases (mptpA and mptpB) and have evaluated its protective efficacy in guinea pigs. We observed that Mtb∆mms was highly attenuated in THP-1 macrophages. Moreover, no bacilli were recovered from the lungs and spleens of guinea pigs after 10 weeks of Mtb∆mms inoculation, although, initially, the mutant exhibited some growth in the spleens. Subsequently, when Mtb∆mms was evaluated for its protective efficacy, we observed that similar to BCG vaccination, Mtb∆mms exhibited a significantly reduced CFU in the lungs of guinea pigs when compared with the unvaccinated animals at 4 weeks after challenge. In addition, our observations at 12 weeks post challenge demonstrated that Mtb∆mms exhibited a more sustainable and superior protection in lungs as compared to BCG. However, the mutant failed to control the hematogenous spread as the splenic bacillary load between Mtb∆mms vaccinated and sham immunized animals was not significantly different. The gross pathological observations and histopathological observations corroborated the bacterial findings. Inspite of disruption of phosphatase genes in MtbΔmms, the lipid profiles of M.tuberculosis and MtbΔmms were identical indicating thereby that the phenotype of the mutant was ascribed to the loss of phosphatase genes and the influence was not related to any alteration in the lipid composition.Conclusions/significanceThis study highlights the importance of M.tuberculosis mutants in imparting protection against pulmonary TB.

Dataset Information

An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs.

Publications

An attenuated quadruple gene mutant of <i>Mycobacterium tuberculosis</i> imparts protection against tuberculosis in guinea pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets