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Assembly and structure of macromolecular complexes involved in bacterial cell wall: biosynthesis and virulence

Grant number: 11/52067-6
Support type:Research Projects - SPEC Program
Duration: July 01, 2012 - July 31, 2017
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Andrea Dessen de Souza e Silva
Grantee:Andrea Dessen de Souza e Silva
Visiting researcher institution: Institut de Biologie Structurale (IBS), France
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil
Associated scholarship(s):14/11980-9 - Identification and structural characterization of new compounds for PBPs inhibition, BP.DR
13/22681-0 - Structural characterization of membrane protein complexes involved in bacterial cell wall biosynthesis, BP.DD
13/01962-0 - Structure and function of bacterial virulence factors, BP.PD
13/02451-0 - Structural characterization of an essential protein complex in cell wall formation, BP.DD

Abstract

The bacterial cell wall is a complex three-dimensional structure that protects the cell from environmental stress, ensures its shape, and plays key roles in cell division and wall elongation processes. In addition, the cell wall serves as an attachment site for a number of virulence factors and secretion systems, that are necessary not only for infection but often for bacterial survival. In the BACWALL project, we will structurally and functionally characterize key macromolecular complexes involved in cell wall biosysnthesis and repair, such as those formed by Penicillin-Binding Proteins, which play key roles in cell wall formation. In addition, we will also tackle the study of bacterial virulence mechanisms which depend on the cell wall for stability and functionality. We will accomplish these goals through the employment of a combination of X-ray crystallography, biochemistry, molecular biology, and electron microscopy. The applicant will be located both at the LNBio (Campinas) and at the Institut de Biologie Structurale (Grenoble, France), and extensive collaborations will be developed with the electron microscopy group at the LNNano (Campinas). In addition, existing collaboration between the group at the IBS and other European institutes (Institut Pateur, Paris; Univ. Utrecht, The Netherlands; iRTSV, Grenoble) will continue throughout BACWALL, allowing the formation of a network that will include the LNBio and LNNano. The availability of a number of key preliminary results suggests that the work proposed here will succeed in revealing key aspects of peptidoglycan assembly machineries and virulence that will be important not only for the drug development field but also for the understanding of general mechanisms of macromolecular complex formation. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
New target for development of innovative antibiotics is revealed 
Research reveals mechanism of bacterial cell division inhibition 
Study indicates that bacteria have rudimentary immune system  
Scientific research funding in São Paulo State from FAPESP reaches more than US$ 430 million  
Laboratory investigates bacterial proteins in the search for new antibiotics 

Scientific publications (9)
(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)
MIYACHIRO, MAYARA M.; GRANATO, DANIELA; TRINDADE, DANIEL MARAGNO; EBEL, CHRISTINE; PAES LEME, ADRIANA FRANCO; DESSEN, ANDREA. Complex Formation between Mur Enzymes from Streptococcus pneumoniae. BIOCHEMISTRY, v. 58, n. 30, p. 3314-3324, JUL 30 2019. Web of Science Citations: 0.
LADDOMADA, FEDERICA; MIYACHIRO, MAYARA M.; JESSOP, MATTHEW; PATIN, DELPHINE; JOB, VIVIANA; MENGIN-LECREULX, DOMINIQUE; LE ROY, ALINE; EBEL, CHRISTINE; BREYTON, CECILE; GUTSCHE, IRINA; DESSEN, ANDREA. The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis. SCIENTIFIC REPORTS, v. 9, MAR 15 2019. Web of Science Citations: 1.
ZOUHIR, SAMIRA; ROBERT-GENTHON, MYLENE; TRINDADE, DANIEL MARAGNO; JOB, VIVIANA; NEDELJKOVIC, MARKO; BREYTON, CECILE; EBEL, CHRISTINE; ATTREE, INA; DESSEN, ANDREA. Assembly of an atypical alpha-macroglobulin complex from &ITPseudomonas aeruginosa&IT. SCIENTIFIC REPORTS, v. 8, JAN 11 2018. Web of Science Citations: 0.
CONTRERAS-MARTEL, CARLOS; MARTINS, ALEXANDRE; ECOBICHON, CHANTAL; TRINDADE, DANIEL MARAGNO; MATTEI, PIERRE-JEAN; HICHAM, SAMIA; HARDOUIN, PIERRE; EL GHACHI, MERIEM; BONECA, IVO G.; DESSEN, ANDREA. Molecular architecture of the PBP2-MreC core bacterial cell wall synthesis complex. NATURE COMMUNICATIONS, v. 8, OCT 3 2017. Web of Science Citations: 9.
ASSIS, L. MAYRINK; NEDELJKOVIC, M.; DESSEN, A. New strategies for targeting and treatment of multi-drug resistant Staphylococcus aureus. DRUG RESISTANCE UPDATES, v. 31, p. 1-14, MAR 2017. Web of Science Citations: 18.
LADDOMADA, FEDERICA; MIYACHIRO, MAYARA M.; DESSEN, ANDREA. Structural Insights into Protein-Protein Interactions Involved in Bacterial Cell Wall Biogenesis. ANTIBIOTICS-BASEL, v. 5, n. 2 JUN 2016. Web of Science Citations: 10.
DA MATA MADEIRA, PAULO VINICIUS; ZOUHIR, SAMIRA; BASSO, PAULINE; NEVES, DAVID; LAUBIER, AURELIE; SALACHA, RICHARD; BLEVES, SOPHIE; FAUDRY, ERIC; CONTRERAS-MARTEL, CARLOS; DESSEN, ANDREA. Structural Basis of Lipid Targeting and Destruction by the Type V Secretion System of Pseudomonas aeruginosa. Journal of Molecular Biology, v. 428, n. 9, A, p. 1790-1803, MAY 8 2016. Web of Science Citations: 9.
WONG, STEVE G.; DESSEN, ANDREA. Structure of a bacterial alpha(2)-macroglobulin reveals mimicry of eukaryotic innate immunity. NATURE COMMUNICATIONS, v. 5, SEP 2014. Web of Science Citations: 17.
NEVES, DAVID; JOB, VIVIANA; DORTET, LAURENT; COSSART, PASCALE; DESSEN, ANDREA. Structure of Internalin InIK from the Human Pathogen Listeria monocytogenes. Journal of Molecular Biology, v. 425, n. 22, p. 4520-4529, NOV 15 2013. Web of Science Citations: 10.

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