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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2005-11-18
pubmed:abstractText
We had previously reported identification of the virS gene of Mycobacterium tuberculosis (Rv3082c) belonging to the AraC family of transcriptional regulators. The 7 genes (Rv3083-Rv3089) which are present divergently to virS (Rv3082c) constitute an operon designated as the mymA operon. Further investigation on the regulation of this operon showed that transcription of the mymA operon is dependent on the presence of VirS protein. A 4-fold induction of the mymA operon promoter occurs specifically in the wild type M. tuberculosis and not in the virS mutant of M. tuberculosis (M.tbDeltavirS) when exposed to acidic pH. Expression of the mymA operon was also induced in infected macrophages by ten-fold over a six-day period. Bioinformatic analysis suggested the involvement of these proteins in the modification of fatty acids required for cell envelope. This was supported by altered colony morphology and cell envelope structure and increased accumulation of C24/C26 fatty acids by M.tbDeltavirS in comparison to the wild type strain. Thus, induction of mymA operon can play an important role in remodeling the envelope of intracellular M. tuberculosis under acidic conditions. Genomic analysis of M. tuberculosis revealed the presence of two tyrosine phosphatase genes--mptpA (Rv2234) and mptpB (Rv0153c). We have characterized both the tyrosine phosphatases of M. tuberculosis. To evaluate the role of MptpB in the pathogenesis of M. tuberculosis we have disrupted mptpB in the genome of M. tuberculosis. The wild type as well as mptpB mutant strain were comparable in their ability to infect and survive in the resting macrophages. However, the mptpB mutant strain was more sensitive to killing as compared to the wild type strain by IFN-gamma activated macrophages. In guinea pig model of tuberculosis an approximately 70-fold reduced bacillary load was observed in the spleen of the animals infected with mptpB mutant strain as compared to the bacillary load in animals infected with the wild type strain at 6 weeks post-infection. These results suggest that mymA operon as well as mptpB gene of M. tuberculosis play an important role in the survival of the pathogen in the host.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1472-9792
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
325-35
pubmed:dateRevised
2009-4-22
pubmed:meshHeading
pubmed-meshheading:16256440-Animals, pubmed-meshheading:16256440-AraC Transcription Factor, pubmed-meshheading:16256440-Bacterial Proteins, pubmed-meshheading:16256440-Computational Biology, pubmed-meshheading:16256440-Gene Expression Regulation, Bacterial, pubmed-meshheading:16256440-Genetic Engineering, pubmed-meshheading:16256440-Genome, Bacterial, pubmed-meshheading:16256440-Guinea Pigs, pubmed-meshheading:16256440-Macrophages, pubmed-meshheading:16256440-Mice, pubmed-meshheading:16256440-Microscopy, Electron, pubmed-meshheading:16256440-Mutation, pubmed-meshheading:16256440-Mycobacterium tuberculosis, pubmed-meshheading:16256440-Operon, pubmed-meshheading:16256440-Promoter Regions, Genetic, pubmed-meshheading:16256440-Protein Tyrosine Phosphatases, pubmed-meshheading:16256440-Tuberculosis, pubmed-meshheading:16256440-Virulence
pubmed:articleTitle
Deciphering the genes involved in pathogenesis of Mycobacterium tuberculosis.
pubmed:affiliation
Department of Biochemistry, University of Delhi South campus, New Delhi-110021, India.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't