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The changes in mycolic acid structures caused byhadCmutation have a dramatic effect on the virulence ofMycobacterium tuberculosis
- Source :
- Molecular Microbiology. 99:794-807
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- Understanding the molecular strategies used by Mycobacterium tuberculosis to invade and persist within the host is of paramount importance to tackle the tuberculosis pandemic. Comparative genomic surveys have revealed that hadC, encoding a subunit of the HadBC dehydratase, is mutated in the avirulent M. tuberculosis H37Ra strain. We show here that mutation or deletion of hadC affects the biosynthesis of oxygenated mycolic acids, substantially reducing their production level. Additionally, it causes the loss of atypical extra-long mycolic acids, demonstrating the involvement of HadBC in the late elongation steps of mycolic acid biosynthesis. These events have an impact on the morphotype, cording capacity and biofilm growth of the bacilli as well as on their sensitivity to agents such as rifampicin. Furthermore, deletion of hadC leads to a dramatic loss of virulence: an almost 4-log drop of the bacterial load in the lungs and spleens of infected immunodeficient mice. Both its unique function and importance for M. tuberculosis virulence make HadBC an attractive therapeutic target for tuberculosis drug development.
- Subjects :
- 0301 basic medicine
chemistry.chemical_classification
Mutation
Tuberculosis
biology
030106 microbiology
Virulence
biology.organism_classification
medicine.disease_cause
medicine.disease
Microbiology
3. Good health
Mycolic acid
Mycobacterium tuberculosis
03 medical and health sciences
chemistry.chemical_compound
Biosynthesis
chemistry
Dehydratase
medicine
Molecular Biology
Rifampicin
medicine.drug
Subjects
Details
- ISSN :
- 0950382X
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Molecular Microbiology
- Accession number :
- edsair.doi...........b6cb6728ee022952ab6e014735158ddc