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Role of bacterial potassium transporters in inflammatory activation process and in macrophages response to infection by Legionella pneumophila

Grant number: 11/51023-5
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2011
Effective date (End): October 31, 2014
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal Investigator:Dario Simões Zamboni
Grantee:Juliana Issa Hori
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Legionella pneumophila is an intracellular gram-negative bacterium responsible for causing a severe pneumonia called Legionnaires' disease. Mice genetic studies contributed to demonstrate that innate immunity receptors present in the cytoplasm of the cell, as Naip5/Birc1 e (a member of family of NLRs receptors) are involved with the control of bacterial infection in macrophages and in vivo. Later, it was demonstrated that other intracellular proteins as Nlrc4 and Asc participate in the formation of inflammasomes that culminate in activation of caspase-1 and restriction of intracellular replication of L. pneumophila. Moreover, it was verified that the activation of caspase-1 mediated by Naip5 and Nlrc4 occurs in response to the C terminal region of L. pneumophila's flagellin. However, macrophages from wild type mice still show activation of caspase-1, even when they are infected with L. pneumophila flagellin mutant, suggesting that there are other agonists involved in the process of cell activation that culminates with the control of L. pneumophila. Through genetic screening in Legionella, we recently identified that bacterial mutants in gene kupA, which encodes a functional K + transporter, resist to innate immunity of macrophages and also are able to multiply inside restrictive host cells (Juliana Issa Hori, PhD thesis and manuscript under review Infect. Immun.). Since K + nas a crucial role in the activation of inflammasomes, it becomes necessary to investigate the role bacterial K + transporters in innate immune recognition and in the activation of inflammasomes in response to intracellular bactéria. Therefore, the purpose of this study is to investigate the role of KupA in the activation of inflammasomes and determine, under physiological conditions, the molecular mechanisms responsible for this activation. (AU)

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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)
HORI, JULIANA I.; PEREIRA, MARCELO S. F.; ROY, CRAIG R.; NAGAI, HIROKI; ZAMBONI, DARIO S.. Identification and functional characterization of K+ transporters encoded by Legionella pneumophila kup genes. Cellular Microbiology, v. 15, n. 12, p. 2006-2019, . (11/22617-4, 12/09363-6, 11/51023-5)
HORI, JULIANA I.; ZAMBONI, DARIO S.; CARRAO, DANIEL B.; GOLDMAN, GUSTAVO HENRIQUE; BERRETTA, ANDRESA A.. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF). Evidence-based Complementary and Alternative Medicine, . (11/51023-5)
ZOCCAL, KARINA F.; SORGI, CARLOS A.; HORI, JULIANA I.; PAULA-SILVA, FRANCISCO W. G.; ARANTES, ELIANE C.; SEREZANI, CARLOS H.; ZAMBONI, DARIO S.; FACCIOLI, LUCIA H.. Opposing roles of LTB4 and PGE(2) in regulating the inflammasome-dependent scorpion venom-induced mortality. NATURE COMMUNICATIONS, v. 7, . (14/07125-6, 11/51023-5, 14/03332-7, 14/04684-4)

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