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

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 biosynthesi...

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Bibliographic Details
Published in:PloS one 2017-06, Vol.12 (6), p.e0179513-e0179513
Main Authors: Kar, Ritika, Nangpal, Prachi, Mathur, Shubhita, Singh, Swati, Tyagi, Anil K
Format: Article
Language:English
Subjects:
Aerosols
Animals
Attenuation
Bacillus Calmette-Guerin vaccine
Bacterial Proteins - genetics
BCG
Biochemistry
Biology and Life Sciences
Biosynthesis
Biotin
Care and treatment
Clinical trials
Disease Models, Animal
Dosage and administration
Enzymes
Genes
Granulomas
Growth
Guinea Pigs
Hypoxia
Immunization
Infections
Medicine and Health Sciences
Microorganisms
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Physical Sciences
Research and Analysis Methods
Survival
Transaminases - genetics
Transcription
Tuberculosis
Tuberculosis - prevention & control
Tuberculosis Vaccines - immunology
Tuberculosis Vaccines - therapeutic use
Vaccines
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0179513