Gene expression can be modulated by transcription factors, which act directly as intracellular signal sensors or via signaling transduction pathways from the external environment. MarR family transcription factors, found in Bacteria and Archaea, act as direct sensors for different signals, controlling virulence, response to oxidative stress, antibiotic resistance and catabolic pathways. Although there are several potential MarR family transcription regulators in Chromobacterium violaceum, only OhrR, involved in resistance to organic hydroperoxides, has been previously studied by our lab. Therefore, we propose to identify and characterize MarR family transcription factors that control virulence in this human opportunistic pathogen, trying to elucidate the activation signals and the genes under regulation of each transcription factor. For this, we will identify the MarR family transcription factors in the genome of C. violaceum, classify them respect the presence of conserved cysteine residues and perform systematic mutagenesis for deletion of many genes encoding these regulators. The phenotype of each mutant strain will be characterized by testing for growth in many conditions and by virulence assays using a mouse model. The regulons of some of these transcription factors, mainly those involved in virulence, will be defined by DNA microarray analyses and by biochemical tests, such as DNA binding assays and site-directed mutagenesis of conserved cysteine residues. Thus, from this systematic analysis of MarR family transcription factors in C. violaceum, we intend to contribute to find novel bacterial virulence regulators.
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