Premium
Rv1675c ( cmr ) regulates intramacrophage and cyclic AMP‐induced gene expression in Mycobacterium tuberculosis ‐complex mycobacteria
Author(s) -
Gazdik Michaela A.,
Bai Guangchun,
Wu Yan,
McDonough Kathleen A.
Publication year - 2009
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06541.x
Subject(s) - regulon , biology , mycobacterium bovis , mycobacterium tuberculosis , gene , promoter , microbiology and biotechnology , regulation of gene expression , gene expression , tuberculosis , genetics , medicine , pathology
Summary Cyclic AMP (cAMP) has recently been shown to be a global regulator of gene expression in Mycobacterium tuberculosis (Mtb). In this study we identified a new cAMP‐associated regulon in Mtb and Mycobacterium bovis BCG, which is distinct from the previously described CRP Mt regulon. Proteomic comparison of wild‐type M. bovis BCG with a Rv1675c ( cmr ) knockout strain showed dysregulated expression of four previously identified proteins encoded by the cAMP‐induced genes (cAIGs) mdh , gro EL2, Rv1265 and PE_PGRS6a. Regulated expression of these four cAIGs also occurred during macrophage infection, and this regulation required cmr in both Mtb and M. bovis BCG. Purified His‐Cmr bound to the DNA sequences upstream of three cAIGs ( mdh , gro EL2, Rv1265) in electrophoretic mobility shift assays, suggesting direct regulation of these genes by Cmr. We also found that low pH stimulated cAMP production in both Mtb and M. bovis BCG, but broadly affected cAIG regulation only in M. bovis BCG. These studies identify Cmr as a transcription factor that regulates cAIGs within macrophages, and suggest that multiple factors affect cAMP‐associated gene regulation in tuberculosis‐complex mycobacteria. cAMP signalling and Cmr‐mediated gene regulation during Mtb infection of macrophages may have implications for TB pathogenesis.