Premium
Targeting IdeR as a Potential Therapy Against Mycobacteriuim tuberculosis Infections
Author(s) -
Monfeli Ryan,
Chou James,
Wisedchaisri Goragot,
Oram Diana,
Holmes Randall,
Hol Wim G. J.,
Beeson Craig
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.667
Subject(s) - mycobacterium tuberculosis , virulence , biology , repressor , microbiology and biotechnology , dna , gene , reporter gene , bacteria , tuberculosis , gene expression , biochemistry , genetics , medicine , pathology
The bacteria Mycobacterium tuberculosis causes the disease tuberculosis, which is a growing worldwide health problem. None of the current antibiotics target IdeR, which is a mycobacterial protein that is an important transcriptional regulator. Partial inactivation of IdeR has been shown to cause reduced viability and virulence. Release of IdeR from mycobacterial repressor sites within the host is essential for bacterial growth and, therefore, we hypothesized that compounds that stabilize IdeR binding to DNA will reduce the virulence gene expression of Mycobacterium tuberculosis . A small peptide, named DOX‐S, was found to stabilize IdeR binding to the mycobacterial FxbA promoter. Modifications to the this DOX‐S peptide have resulted in peptides that are capable of enhancing IdeR binding to target DNA sequences within E. coli using a b‐galactosidase reporter system as a model for virulence gene expression. An alternative to enhancing IdeR binding to DNA is the prevention of DNA binding. Very recently we have also developed compounds that are able to prevent IdeR from binding to target mycobacterial DNA sequences using the aforementioned E coli reporter assay. These compounds have been tested for their ability to inhibit growth in Mycobacterium tuberculosis . Research is supported by NIH grants CA65656 (W.G.J.H.) and AI14107 (R.K.H.).