BioA mutant of Mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs.

Ritika Kar,Prachi Nangpal,Shubhita Mathur,Swati Singh,Anil K Tyagi,Ann Rawkins

doi:10.1371/journal.pone.0179513

Ritika Kar, Prachi Nangpal + Show 4 more

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https://doi.org/10.1371/journal.pone.0179513

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Abstract

Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette–Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally. Immunization with MtbΔbioA conferred significant protection in guinea pigs against an aerosol challenge with virulent M. tuberculosis, when compared with the unvaccinated animals. Booster immunization with MtbΔbioA offered no advantage over a single immunization. These experiments demonstrate the vaccinogenic potential of the attenuated M. tuberculosis bioA mutant against tuberculosis.

Highlights

The vaccine Bacillus Calmette–Guerin (BCG), an attenuated strain of Mycobacterium bovis, has been widely administered since 1921
A study comparing BCG and M. tuberculosis substrains has shown that a large number of T-cell epitopes are missing from BCG substrains but are present in all five M. tuberculosis strains employed for the comparative analysis [8]
Disruption of the bioA gene in M. tuberculosis was confirmed by polymerase chain reaction (PCR) analysis by using bioA gene specific primers (Fig 1a and 1b, Table 1)

Summary

Introduction

The vaccine Bacillus Calmette–Guerin (BCG), an attenuated strain of Mycobacterium bovis, has been widely administered since 1921. BCG protects children against severe forms of tuberculosis (TB) but demonstrates highly variable efficacy (0–80%) against adult pulmonary tuberculosis in different field trials with poor efficacy in high TB burden countries, in general [1,2,3,4,5]. There is a clear need for a new effective TB vaccine and a number of candidate vaccines based on several different approaches are currently being evaluated in clinical trials [6]. One of the most advanced TB vaccine candidate that attempted to boost the efficacy of BCG was unable to induce any additional efficacy over BCG in a recent human clinical trial [7]. One promising approach of vaccine development against TB is the generation of attenuated Mycobacterium tuberculosis mutant strains.

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