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Grant number: 16/05203-5
Support Opportunities:Regular Research Grants
Duration: September 01, 2016 - February 28, 2019
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal Investigator:Frederico José Gueiros Filho
Grantee:Frederico José Gueiros Filho
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil


A crucial but often overlooked aspect of cell biogenesis and survival is the need for precise coordination between the biosynthesis of its macromolecular constituents. In the case of bacterial cells, this means producing appropriate amounts of four classes of macromolecules : nucleic acids, proteins, lipids and the polysaccharides of the cell wall. The molecular basis of coordination is well known in some cases. In others it is still mysterious. In this project we propose to investigate how Gram-positive bacteria coordinate lipid and membrane synthesis with its other biosynthetic activities and in response to environmental conditions and the different events of the cell cycle. We plan to focus on two principal aspects: 1) the role of the enzyme PlsX in the coupling of fatty acid and phospholipids synthesis, and 2) the role of the signaling nucleotide ppGpp in the two-way coordination between lipid synthesis and cell growth. To achieve these goals we will apply modern fluorescence microscopy, microbial genetics and protein biochemistry to determine how PlsX associates with the cell membrane and how this affects its enzymatic activity and regulation. A similarly broad array of approaches will also be deployed to study how lipid starvation triggers the activation of the ppGpp synthetase RelA, and how this nucleotide helps cells stay alive in the absence of lipid synthesis Finally, we will set up assays and carry out small molecule screens for inhibitors of PlsX and RelA. Because proper control of lipid metabolism is essential for survival, the discoveries from this project should reveal potential novel targets for antibiotics. (AU)

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Scientific publications (5)
(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)
CAUZ, ANA C. G.; CARRETERO, GUSTAVO P. B.; SARAIVA, GREICE K. V.; PARK, PETER; MORTARA, LAURA; CUCCOVIA, IOLANDA M.; BROCCHI, MARCELO; GUEIROS-FILHO, FREDERICO J.. Violacein Targets the Cytoplasmic Membrane of Bacteria. ACS INFECTIOUS DISEASES, v. 5, n. 4, p. 539-549, . (13/08166-5, 16/05203-5, 12/20116-0)
SASTRE, DIEGO E.; BASSO, LUIS G. M.; TRASTOY, BEATRIZ; CIFUENTE, JAVIER O.; CONTRERAS, XABIER; GUEIROS-FILHO, FREDERICO; DE MENDOZA, DIEGO; NAVARRO, MARCOS V. A. S.; GUERIN, MARCELO E.. Membrane fluidity adjusts the insertion of the transacylase PlsX to regulate phospholipid biosynthesis in Gram-positive bacteria. Journal of Biological Chemistry, v. 295, n. 7, p. 2136-2147, . (16/05203-5, 15/21583-0, 14/00206-0, 14/13411-1)
SASTRE, DIEGO E.; PULSCHEN, ANDRE A.; BASSO, LUIS G. M.; PARIENTE, JHONATHAN S. BENITES; MARQUES NETTO, CATERINA G. C.; MACHINANDIARENA, FEDERICO; ALBANESI, DANIELA; NAVARRO, MARCOS V. A. S.; DE MENDOZA, DIEGO; GUEIROS-FILHO, FREDERICO J.. The phosphatidic acid pathway enzyme PlsX plays both catalytic and channeling roles in bacterial phospholipid synthesis. Journal of Biological Chemistry, v. 295, n. 7, p. 2148-2159, . (16/05203-5, 15/21583-0, 14/00206-0, 14/13411-1)
YU, YUANCHEN; ZHOU, JINSHENG; GUEIROS-FILHO, FREDERICO J.; KEARNS, DANIEL B.; JACOBSON, STEPHEN C.. Noc Corrals Migration of FtsZ Protofilaments during Cytokinesis in Bacillus subtilis. MBIO, v. 12, n. 1, . (16/05203-5)
YU, YUANCHEN; DEMPWOLFF, FELIX; OSHIRO, REID T.; GUEIROS-FILHO, FREDERICO J.; JACOBSON, STEPHEN C.; KEARNS, DANIEL B.. The Division Defect of a Bacillus subtilis minD noc Double Mutant Can Be Suppressed by Spx-Dependent and Spx-Independent Mechanisms. Journal of Bacteriology, v. 203, n. 18, . (16/05203-5)

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