The Fur family of transcription factors and the response to iron and zinc in Chromobacterium violaceum

Abstract

The transition metals iron and zinc are essential micronutrients to all forms of life. Either in the environment or in the host, these metals are almost unavailable to bacteria, but paradoxically are toxic in an overload inside the cell. The scarcity of iron and zinc compelled by the host is a signal for regulation of virulence genes, via transcription factors of Fur family, in several bacterial pathogens. In this project, we aim to characterize the response to iron and zinc limitation and the role of the transcription factors Fur and Zur in the bacterium Chromobacterium violaceum, an occasional opportunistic pathogen of humans generally found in water and soil. Due to the difficult diagnosis and the treatment often equivocated, the infections of C. violaceum present high mortality rates. The genome sequencing of this bacterium indicates its potential flexibility to environmental adaptation, but there are very few functional studies yet. To pointing out the role of Fur and Zur in the virulence and physiology of C. violaceum, mutant strains will be obtained and these strains will be characterized in vitro in culture medium and in vivo in infection mouse models. The identification of the Fur and Zur regulons and of the iron and zinc stimulons will be performed by RNA-Seq, followed by validation of expression profiles and DNA binding-sites. Selected genes of each regulon, which encode to potential virulence factors, will be subjected to further characterization. In this sense, the findings obtained from this work will contribute to understand how C. violaceum fight against the nutritional immunity imposed by the host using its iron and zinc responsive regulatory systems.