Scholarship 17/03342-0 - Regulação da expressão gênica, Fatores de transcrição - BV FAPESP
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The Fur family of transcription factors and the response to iron and zinc in Chromobacterium violaceum

Grant number: 17/03342-0
Support Opportunities:Scholarships in Brazil - Doctorate
Start date: December 01, 2017
End date: September 30, 2021
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal Investigator:José Freire da Silva Neto
Grantee:Renato Elias Rodrigues de Souza Santos
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/20435-9 - Transcription factors of Chromobacterium violaceum: integrating signaling pathways, regulons and pathogenicity, AP.JP

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.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SANTOS, RENATO E. R. S.; DA SILVA JUNIOR, WALDIR P.; HARRISON, SIMONE; SKAAR, ERIC P.; CHAZIN, WALTER J.; DA SILVA NETO, JOSE F.. The Zinc Transporter ZnuABC Is Critical for the Virulence of Chromobacterium violaceum and Contributes to Diverse Zinc-Dependent Physiological Processes. Infection and Immunity, v. 89, n. 11, . (17/03342-0, 20/00259-8, 18/01388-6, 18/14737-9)
RODRIGUES DE SOUZA SANTOS, RENATO ELIAS; BATISTA, BIANCA BONTEMPI; DA SILVA NETO, JOSE FREIRE. Ferric Uptake Regulator Fur Coordinates Siderophore Production and Defense against Iron Toxicity and Oxidative Stress and Contributes to Virulence in Chromobacterium violaceum. Applied and Environmental Microbiology, v. 86, n. 21, . (17/03342-0, 18/01388-6, 20/00259-8, 18/19058-2)
BATISTA, BIANCA BONTEMPI; RODRIGUES DE SOUZA SANTOS, RENATO ELIAS; RICCI-AZEVEDO, RAFAEL; SILVA NETO, JOSE FREIRE. Production and Uptake of Distinct Endogenous Catecholate-Type Siderophores Are Required for Iron Acquisition and Virulence in Chromobacterium violaceum. Infection and Immunity, v. 87, n. 12, . (18/01388-6, 12/20435-9, 17/03342-0, 17/02998-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANTOS, Renato Elias Rodrigues de Souza. The Fur family of transcription factors and the response to iron and zinc in Chromobacterium violaceum. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.