Andrea Dessen de Souza e Silva

Pós-doutorado

Formação complementar

Idiomas

Áreas de atuação

Participação em eventos

Orientou

Produções bibliográficas

• SHIRAKAWA, KARINA T. ; SALA, FERNANDA ANGÉLICA ; MIYACHIRO, MAYARA M. ; JOB, VIVIANA ; TRINDADE, DANIEL MARAGNO ; Dessen, Andréa . Architecture and genomic arrangement of the MurE-MurF bacterial cell wall biosynthesis complex. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA , v. 120, p. 1, 2023.

• BONHOMME, SARAH ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andréa ; MACHEBOEUF, PAULINE . Architecture of a PKS-NRPS hybrid megaenzyme involved in the biosynthesis of the genotoxin colibactin. STRUCTURE , v. 31, p. 700-712.e4, 2023.

• STALOCH, BRENDON EGON KORMANN ; NIERO, HENRIQUE ; FREITAS, ROBERT CARDOSO DE ; BALLONE, PATRICIA ; RODRIGUES-COSTA, FERNANDA ; TRIVELLA, DANIELA BARRETTO BARBOSA ; Dessen, Andréa ; SILVA, MARCUS ADONAI CASTRO DA ; LIMA, ANDRÉ OLIVEIRA DE SOUZA . Draft genome sequence of Psychrobacter nivimaris LAMA 639 and its biotechnological potential. DATA IN BRIEF , v. 41, p. 107927, 2022.

• FLANDERS, PARKER L. ; CONTRERAS-MARTEL, CARLOS ; BROWN, NATHANIEL W. ; SHIRLEY, JOSHUA D. ; MARTINS, ALEXANDRE ; NAUTA, KELSIE N. ; Dessen, Andréa ; CARLSON, ERIN E. ; AMBROSE, ELIZABETH A. . Combined Structural Analysis and Molecular Dynamics Reveal Penicillin-Binding Protein Inhibition Mode with β-Lactones. ACS Chemical Biology , v. 17, p. 3110-3120, 2022.

• DE FELÍCIO, RAFAEL ; BALLONE, PATRICIA ; BAZZANO, CRISTINA FREITAS ; ALVES, LUIZ F. G. ; SIGRIST, RENATA ; INFANTE, GINA POLO ; NIERO, HENRIQUE ; RODRIGUES-COSTA, FERNANDA ; FERNANDES, ARTHUR ZANETTI NUNES ; TONON, LUCIANE A. C. ; PARADELA, LUCIANA S. ; COSTA, RENNA KAROLINE ELOI ; DIAS, SANDRA MARTHA GOMES ; Dessen, Andréa ; TELLES, GUILHERME P. ; DA SILVA, MARCUS ADONAI CASTRO ; LIMA, ANDRE OLIVEIRA DE SOUZA ; TRIVELLA, DANIELA BARRETTO BARBOSA . Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions. METABOLITES , v. 11, p. 107, 2021.

• BONHOMME, SARAH ; Dessen, Andréa ; MACHEBOEUF, PAULINE . The inherent flexibility of type I non-ribosomal peptide synthetase multienzymes drives their catalytic activities. Open Biology , v. 11, p. 200386, 2021.

• ZOUHIR, SAMIRA ; CONTRERAS'MARTEL, CARLOS ; MARAGNO TRINDADE, DANIEL ; ATTRÉE, INA ; Dessen, Andréa ; MACHEBOEUF, PAULINE . MagC is a NplC/P60-like member of the α-2-macroglobulin Mag complex of that interacts with peptidoglycan. FEBS LETTERS , v. 595, p. 2034-2046, 2021.

• MARTINS, ALEXANDRE ; CONTRERAS-MARTEL, CARLOS ; JANET-MAITRE, MANON ; MIYACHIRO, MAYARA M. ; ESTROZI, LEANDRO F. ; TRINDADE, DANIEL MARAGNO ; MALOSPIRITO, CAÍQUE C. ; RODRIGUES-COSTA, FERNANDA ; IMBERT, LIONEL ; JOB, VIVIANA ; SCHOEHN, GUY ; ATTRÉE, INA ; Dessen, Andréa . Self-association of MreC as a regulatory signal in bacterial cell wall elongation. Nature Communications , v. 12, p. 2987, 2021.

• SILVA, YURI RAFAEL DE OLIVEIRA ; CONTRERAS'MARTEL, CARLOS ; MACHEBOEUF, PAULINE ; Dessen, Andréa . Bacterial secretins: Mechanisms of assembly and membrane targeting. PROTEIN SCIENCE , v. 29, p. 893-904, 2020.

• RODRIGUES-COSTA, FERNANDA ; SLIVINSKI, JULIANO ; IÓCA, LAURA P. ; BERTONHA, ARIANE F. ; DE FELÍCIO, RAFAEL ; CUNHA, MARCOS GUILHERME DA ; DA MATA MADEIRA, PAULO VINICIUS ; CAUZ, ANA C.G. ; TRINDADE, DANIEL MARAGNO ; FREIRE, VÍTOR F. ; ROPKE, CRISTINA DISLICH ; GALES, ANA ; BROCCHI, MARCELO ; FERREIRA, ANTÔNIO G. ; GUEIROS-FILHO, FREDERICO ; TRIVELLA, DANIELA BARRETTO BARBOSA ; BERLINCK, ROBERTO G.S. ; Dessen, Andréa . Merulinic acid C overcomes gentamicin resistance in Enterococcus faecium. BIOORGANIC CHEMISTRY , v. 100, p. 103921, 2020.

• BERTRAND, QUENTIN ; JOB, VIVIANA ; MAILLARD, ANTOINE P. ; IMBERT, LIONEL ; TEULON, JEAN-MARIE ; FAVIER, ADRIEN ; PELLEQUER, JEAN-LUC ; HUBER, PHILIPPE ; ATTRÉE, INA ; Dessen, Andréa . Exolysin (ExlA) from Pseudomonas aeruginosa Punctures Holes into Target Membranes Using a Molten Globule Domain. JOURNAL OF MOLECULAR BIOLOGY , v. 432, p. 4466-4480, 2020.

• LADDOMADA, FEDERICA ; MIYACHIRO, MAYARA M. ; JESSOP, MATTHEW ; PATIN, DELPHINE ; JOB, VIVIANA ; MENGIN-LECREULX, DOMINIQUE ; LE ROY, ALINE ; EBEL, CHRISTINE ; BREYTON, CÉCILE ; GUTSCHE, IRINA ; Dessen, Andréa . The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis. Scientific Reports , v. 9, p. 4656, 2019.

• LOMBARDI, CHARLOTTE ; TOLCHARD, JAMES ; BOUILLOT, STEPHANIE ; SIGNOR, LUCA ; GEBUS, CAROLINE ; LIEBL, DAVID ; FENEL, DAPHNA ; TEULON, JEAN-MARIE ; BROCK, JULIANE ; HABENSTEIN, BIRGIT ; PELLEQUER, JEAN-LUC ; FAUDRY, ERIC ; LOQUET, ANTOINE ; ATTRÉE, INA ; Dessen, Andréa ; JOB, VIVIANA . Structural and Functional Characterization of the Type Three Secretion System (T3SS) Needle of Pseudomonas aeruginosa. Frontiers in Microbiology , v. 10, p. 573, 2019.

• HOWARD, S. PETER ; ESTROZI, LEANDRO F. ; BERTRAND, QUENTIN ; CONTRERAS-MARTEL, CARLOS ; STROZEN, TIMOTHY ; JOB, VIVIANA ; MARTINS, ALEXANDRE ; FENEL, DAPHNA ; SCHOEHN, GUY ; Dessen, Andréa . Structure and assembly of pilotin-dependent and -independent secretins of the type II secretion system. PLoS Pathogens , v. 15, p. e1007731, 2019.

• MIYACHIRO, MAYARA M. ; GRANATO, DANIELA ; TRINDADE, DANIEL MARAGNO ; EBEL, CHRISTINE ; PAES LEME, ADRIANA FRANCO ; Dessen, Andréa . Complex Formation between Mur Enzymes from Streptococcus pneumoniae. BIOCHEMISTRY , v. 58, p. 3314-3324, 2019.

• PAGLIUSO, ALESSANDRO ; THAM, TO NAM ; ALLEMAND, ERIC ; ROBERTIN, STEVENS ; DUPUY, BRUNO ; BERTRAND, QUENTIN ; BÉCAVIN, CHRISTOPHE ; KOUTERO, MIKAEL ; NAJBURG, VALÉRIE ; NAHORI, MARIE-ANNE ; TANGY, FRÉDÉRIC ; STAVRU, FABRIZIA ; BESSONOV, SERGEY ; Dessen, Andréa ; MUCHARDT, CHRISTIAN ; LEBRETON, ALICE ; KOMAROVA, ANASTASSIA V. ; COSSART, PASCALE . An RNA-Binding Protein Secreted by a Bacterial Pathogen Modulates RIG-I Signaling. Cell Host & Microbe , v. 26, p. 823-835.e11, 2019.

• ZOUHIR, SAMIRA ; ROBERT-GENTHON, MYLÈNE ; TRINDADE, DANIEL MARAGNO ; JOB, VIVIANA ; NEDELJKOVI', MARKO ; BREYTON, CÉCILE ; EBEL, CHRISTINE ; ATTRÉE, INA ; Dessen, Andréa . Assembly of an atypical α-macroglobulin complex from Pseudomonas aeruginosa. Scientific Reports , v. 8, p. 1, 2018.

• DORTET, LAURENT ; LOMBARDI, CHARLOTTE ; CRETIN, FRANÇOIS ; Dessen, Andréa ; FILLOUX, ALAIN . Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome. Nature Microbiology , v. 3, p. 378-386, 2018.

• ASSIS, L. MAYRINK ; NEDELJKOVI', M. ; DESSEN, A. . New strategies for targeting and treatment of multi-drug resistant Staphylococcus aureus. DRUG RESISTANCE UPDATES , v. 31, p. 1-14, 2017.

• CONTRERAS-MARTEL, CARLOS ; MARTINS, ALEXANDRE ; ECOBICHON, CHANTAL ; TRINDADE, DANIEL MARAGNO ; MATTEÏ, PIERRE-JEAN ; HICHAM, SAMIA ; HARDOUIN, PIERRE ; GHACHI, MERIEM EL ; BONECA, IVO G. ; Dessen, Andréa . Molecular architecture of the PBP2-MreC core bacterial cell wall synthesis complex. Nature Communications , v. 8, p. 776, 2017.

• LADDOMADA, FEDERICA ; MIYACHIRO, MAYARA ; Dessen, Andréa . Structural Insights into Protein-Protein Interactions Involved in Bacterial Cell Wall Biogenesis. Antibiotics , v. 5, p. 14, 2016.

• ?INK, ROMAN ; KOTNIK, MIHA ; ZEGA, ANAMARIJA ; BARRETEAU, HÉLÈNE ; GOBEC, STANISLAV ; BLANOT, DIDIER ; Dessen, Andréa ; CONTRERAS-MARTEL, CARLOS . Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement Revisited. Plos One , v. 11, p. e0152075, 2016.

• DA MATA MADEIRA, PAULO VINICIUS ; ZOUHIR, SAMIRA ; BASSO, PAULINE ; NEVES, DAVID ; LAUBIER, AURÉLIE ; SALACHA, RICHARD ; BLEVES, SOPHIE ; FAUDRY, ERIC ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andréa . Structural Basis of Lipid Targeting and Destruction by the Type V Secretion System of Pseudomonas aeruginosa. JOURNAL OF MOLECULAR BIOLOGY , v. 428, p. 1790-1803, 2016.

• BISSON-FILHO, ALEXANDRE W. ; DISCOLA, KAREN F. ; CASTELLEN, PATRÍCIA ; BLASIOS, VALDIR ; MARTINS, ALEXANDRE ; SFORÇA, MAURÍCIO L. ; GARCIA, WANIUS ; ZERI, ANA CAROLINA M. ; ERICKSON, HAROLD P. ; Dessen, Andréa ; GUEIROS-FILHO, FREDERICO J. . FtsZ filament capping by MciZ, a developmental regulator of bacterial division. Proceedings of the National Academy of Sciences of the United States of America , v. 112, p. 201414242, 2015.

• SHAIK, MD MUNAN ; LOMBARDI, CHARLOTTE ; MARAGNO TRINDADE, DANIEL ; FENEL, DAPHNA ; SCHOEHN, GUY ; DI GUILMI, ANNE MARIE ; Dessen, Andréa . A structural snapshot of type II pilus formation in Streptococcus pneumoniae. Journal of Biological Chemistry (Online) , v. 290, p. jbc.M115.647834, 2015.

• DISCOLA, K. F. ; FORSTER, A. ; BOULAY, F. ; SIMORRE, J.-P. ; ATTREE, I. ; Dessen, A. ; JOB, V. . Membrane and Chaperone Recognition by the Major Translocator Protein PopB of the Type III Secretion System of Pseudomonas aeruginosa. The Journal of Biological Chemistry (Print) , v. 289, p. 3591-3601, 2014.

• NIKOLAIDIS, IOULIA ; FAVINI-STABILE, SANDY ; Dessen, Andrea . Resistance to antibiotics targeted to the bacterial cell wall. Protein Science , v. 23, p. 243-259, 2014.

• TOSI, TOMMASO ; ESTROZI, LEANDRO F. ; JOB, VIVIANA ; GUILVOUT, INGRID ; PUGSLEY, ANTHONY P. ; SCHOEHN, GUY ; Dessen, Andréa . Structural Similarity of Secretins from Type II and Type III Secretion Systems. Structure (London) , v. 22, p. 1348-1355, 2014.

• WONG, STEVE G. ; Dessen, Andréa . Structure of a bacterial α2-macroglobulin reveals mimicry of eukaryotic innate immunity. Nature Communications , v. 5, p. 4917, 2014.

• SHAIK, M. M. ; MACCAGNI, A. ; TOURCIER, G. ; DI GUILMI, A. M. ; DESSEN, A. . Structural Basis of Pilus Anchoring by the Ancillary Pilin RrgC of Streptococcus pneumoniae. The Journal of Biological Chemistry (Print) , v. 289, p. 16988-16997, 2014.

• TOSI, TOMMASO ; PFLUG, ALEXANDER ; DISCOLA, KAREN F. ; NEVES, DAVID ; Dessen, Andréa . Structural basis of eukaryotic cell targeting by type III secretion system (T3SS) effectors. Research in Microbiology (Paris) , v. 164, p. 605, 2013.

• HRAST, MARTINA ; TURK, SAMO ; SOSIč ; KNEZ, DAMIJAN ; RANDALL, CHRISTOPHER P. ; BARRETEAU, HÉLÈNE ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andréa ; O'NEILL, ALEX J. ; MENGIN-LECREULX, DOMINIQUE ; BLANOT, DIDIER ; GOBEC, STANISLAV . Structure-activity relationships of new cyanothiophene inhibitors of the essential peptidoglycan biosynthesis enzyme MurF. European Journal of Medicinal Chemistry , v. 66, p. 32-45, 2013.

• FAVINI-STABILE, SANDY ; CONTRERAS-MARTEL, CARLOS ; THIELENS, NICOLE ; Dessen, Andréa . MreB and MurG as scaffolds for the cytoplasmic steps of peptidoglycan biosynthesis. Environmental Microbiology (Print) , v. 15, p. 3218-3228, 2013.

• ROBERT-GENTHON, M. ; CASABONA, M. G. ; NEVES, D. ; COUTE, Y. ; CICERON, F. ; ELSEN, S. ; Dessen, A. ; ATTREE, I. . Unique Features of a Pseudomonas aeruginosa  2-Macroglobulin Homolog. mBio (Online) , v. 4, p. e00309-13-e00309-13, 2013.

• NEVES, DAVID ; JOB, VIVIANA ; DORTET, LAURENT ; COSSART, PASCALE ; Dessen, Andréa . Structure of Internalin InlK from the Human Pathogen Listeria monocytogenes. Journal of Molecular Biology , v. 425, p. 4520-4529, 2013.

• RUANE, K. M. ; LLOYD, A. J. ; FULOP, V. ; DOWSON, C. G. ; BARRETEAU, H. ; BONIFACE, A. ; DEMENTIN, S. ; BLANOT, D. ; MENGIN-LECREULX, D. ; GOBEC, S. ; Dessen, A. ; ROPER, D. I. . Specificity Determinants for Lysine Incorporation in Staphylococcus aureus Peptidoglycan as Revealed by the Structure of a MurE Enzyme Ternary Complex. The Journal of Biological Chemistry (Print) , v. 288, p. 33439-33448, 2013.

• LEBRETON, A. ; JOB, V. ; RAGON, M. ; LE MONNIER, A. ; DESSEN, A. ; COSSART, P. ; BIERNE, H. . Structural Basis for the Inhibition of the Chromatin Repressor BAHD1 by the Bacterial Nucleomodulin LntA. mBio (Online) , v. 5, p. e00775-13-e00775-13, 2013.

• NEVES, DAVID ; ESTROZI, LEANDRO F. ; JOB, VIVIANA ; GABEL, FRANK ; SCHOEHN, GUY ; Dessen, Andréa . Conformational States of a Bacterial α2-Macroglobulin Resemble Those of Human Complement C3. Plos One , v. 7, p. e35384, 2012.

• GENDRIN, CLAIRE ; CONTRERAS-MARTEL, CARLOS ; BOUILLOT, STÉPHANIE ; ELSEN, SYLVIE ; LEMAIRE, DAVID ; SKOUFIAS, DIMITRIOS A. ; HUBER, PHILIPPE ; ATTREE, INA ; Dessen, Andréa . Structural Basis of Cytotoxicity Mediated by the Type III Secretion Toxin ExoU from Pseudomonas aeruginosa. PLoS Pathogens (Online) , v. 8, p. e1002637, 2012.

• NIKOLAIDIS, IOULIA ; IZORÉ, THIERRY ; JOB, VIVIANA ; THIELENS, NICOLE ; BREUKINK, EEFJAN ; Dessen, Andréa . Calcium-Dependent Complex Formation Between PBP2 and Lytic Transglycosylase SltB1 of. Microbial Drug Resistance (Larchmont, N.Y.) , v. 18, p. 298-305, 2012.

• NEVES, DAVID ; Dessen, Andréa . Microbiology: Sensing stability. Nature Chemical Biology , v. 8, p. 681-682, 2012.

• EL MORTAJI, LAMYA ; CONTRERAS'MARTEL, CARLOS ; MOSCHIONI, MONICA ; FERLENGHI, ILARIA ; MANZANO, CLOTHILDE ; VERNET, THIERRY ; Dessen, Andrea ; DI GUILMI, ANNE MARIE . The full-length major pilin RrgB crystallizes in a fibre-like structure, which presents the D1 isopeptide bond and provides details on the mechanism of pilus polymerization. Biochemical Journal (London. 1984) , v. 441, p. 833-841, 2012.

• INGLIS, STEVEN R. ; STRIEKER, MATTHIAS ; RYDZIK, ANNA M. ; Dessen, Andréa ; SCHOFIELD, CHRISTOPHER J. . A boronic-acid-based probe for fluorescence polarization assays with penicillin binding proteins and β-lactamases. Analytical Biochemistry (Print) , v. 420, p. 41-47, 2012.

• TOSI, TOMMASO ; NICKERSON, NICHOLAS N. ; MOLLICA, LUCA ; JENSEN, MALENE RINGKJØBING ; BLACKLEDGE, MARTIN ; BARON, BRUNO ; ENGLAND, PATRICK ; PUGSLEY, ANTHONY P. ; Dessen, Andréa . Pilotin-secretin recognition in the type II secretion system of Klebsiella oxytoca. Molecular Microbiology (Print) , v. 82, p. 1422-1432, 2011.

• ZIDAR, NACE ; TOMA'I', TIHOMIR ; 'INK, ROMAN ; KOVA', ANDREJA ; PATIN, DELPHINE ; BLANOT, DIDIER ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andréa ; PREMRU, MANICA MÜLLER ; ZEGA, ANAMARIJA ; GOBEC, STANISLAV ; MA'I', LUCIJA PETERLIN ; KIKELJ, DANIJEL . New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: Design, synthesis, crystal structures, and biological evaluation. European Journal of Medicinal Chemistry , v. 46, p. 5512-5523, 2011.

• NICKERSON, N. N. ; TOSI, T. ; Dessen, A. ; BARON, B. ; RAYNAL, B. ; ENGLAND, P. ; PUGSLEY, A. P. . Outer Membrane Targeting of Secretin PulD Protein Relies on Disordered Domain Recognition by a Dedicated Chaperone. Journal of Biological Chemistry (Online) , v. 286, p. 38833-38843, 2011.

• IZORÉ, THIERRY ; PERDU, CAROLINE ; JOB, VIVIANA ; ATTREE, INA ; FAUDRY, ERIC ; Dessen, Andréa . Structural Characterization and Membrane Localization of ExsB from the Type III Secretion System (T3SS) of Pseudomonas aeruginosa. Journal of Molecular Biology , v. 413, p. 236-246, 2011.

• EL GHACHI, MERIEM ; MATTEÏ, PIERRE-JEAN ; ECOBICHON, CHANTAL ; MARTINS, ALEXANDRE ; HOOS, SYLVIANE ; SCHMITT, CHRISTINE ; COLLAND, FRÉDÉRIC ; EBEL, CHRISTINE ; PRÉVOST, MARIE-CHRISTINE ; GABEL, FRANK ; ENGLAND, PATRICK ; Dessen, Andréa ; BONECA, IVO G. . Characterization of the elongasome core PBP2¿:¿MreC complex of Helicobacter pylori. Molecular Microbiology (Print) , v. 82, p. 68-86, 2011.

• CONTRERAS-MARTEL, CARLOS ; AMOROSO, ANA ; WOON, ESTHER C. Y. ; ZERVOSEN, ASTRID ; INGLIS, STEVEN ; MARTINS, ALEXANDRE ; VERLAINE, OLIVIER ; RYDZIK, ANNA M. ; JOB, VIVIANA ; LUXEN, ANDRÉ ; JORIS, BERNARD ; SCHOFIELD, CHRISTOPHER J. ; Dessen, Andréa . Structure-Guided Design of Cell Wall Biosynthesis Inhibitors That Overcome β-Lactam Resistance in (MRSA). ACS Chemical Biology , v. 6, p. 943-951, 2011.

• SZETO, T. H. ; Dessen, A. ; PELICIC, V. . Structure/Function Analysis of Neisseria meningitidis PilW, a Conserved Protein That Plays Multiple Roles in Type IV Pilus Biology. Infection and Immunity (Print) , v. 79, p. 3028-3035, 2011.

• TOMAS'IC', TIHOMIR ; ZIDAR, NACE ; S'INK, ROMAN ; KOVAC', ANDREJA ; BLANOT, DIDIER ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andre'a ; MU'LLER-PREMRU, MANICA ; ZEGA, ANAMARIJA ; GOBEC, STANISLAV ; KIKELJ, DANIJEL ; PETERLIN MAS'IC', LUCIJA . Structure-Based Design of a New Series of -Glutamic Acid Based Inhibitors of Bacterial UDP- -acetylmuramoyl- -alanine: -glutamate Ligase (MurD). Journal of Medicinal Chemistry , v. 54, p. 4600-4610, 2011.

• IZORÉ, THIERRY ; JOB, VIVIANA ; Dessen, Andréa . Biogenesis, Regulation, and Targeting of the Type III Secretion System. Structure (London) , v. 19, p. 603-612, 2011.

• SOSI', IZIDOR ; BARRETEAU, HÉLÈNE ; SIM'I', MIHAEL ; 'INK, ROMAN ; CESAR, JO'KO ; ZEGA, ANAMARIJA ; GRDADOLNIK, SIMONA GOLI' ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andréa ; AMOROSO, ANA ; JORIS, BERNARD ; BLANOT, DIDIER ; GOBEC, STANISLAV . Second-generation sulfonamide inhibitors of d-glutamic acid-adding enzyme: Activity optimisation with conformationally rigid analogues of d-glutamic acid. European Journal of Medicinal Chemistry , v. 46, p. 2880-2894, 2011.

• LEBRETON, A. ; LAKISIC, G. ; JOB, V. ; FRITSCH, L. ; THAM, T. N. ; CAMEJO, A. ; MATTEI, P.-J. ; REGNAULT, B. ; NAHORI, M.-A. ; CABANES, D. ; GAUTREAU, A. ; AIT-SI-ALI, S. ; Dessen, A. ; COSSART, P. ; BIERNE, H. . A Bacterial Protein Targets the BAHD1 Chromatin Complex to Stimulate Type III Interferon Response. Science (New York, N.Y.: Online) , v. 331, p. 1319-1321, 2011.

• MACHEBOEUF, P. ; PIUZZI, M. ; FINET, S. ; BONTEMS, F. ; PÉREZ, J. ; Dessen, A. ; VACHETTE, P. . Solution X-ray scattering study of a full-length class A penicillin-binding protein. Biochemical and Biophysical Research Communications (Print) , v. 405, p. 107-111, 2011.

• MATTEÏ, PIERRE-JEAN ; FAUDRY, ERIC ; JOB, VIVIANA ; IZORÉ, THIERRY ; ATTREE, INA ; Dessen, Andréa . Membrane targeting and pore formation by the type III secretion system translocon. The FEBS Journal (Print) , v. 278, p. 414-426, 2011.

• GENDRIN, CLAIRE ; SARRAZIN, STÉPHANE ; BONNAFFÉ, DAVID ; JAULT, JEAN-MICHEL ; LORTAT-JACOB, HUGUES ; Dessen, Andréa . Hijacking of the Pleiotropic Cytokine Interferon-γ by the Type III Secretion System of Yersinia pestis. Plos One , v. 5, p. e15242, 2010.

• Dessen, Andréa ; XU, WENQING . Structural biology of protein functional regulation. Current Opinion in Structural Biology , v. 20, p. 711-713, 2010.

• MATTEï, PIERRE-JEAN ; DESSEN, ANDRéA ; NEVES, DAVID . Bridging cell wall biosynthesis and bacterial morphogenesis. Current Opinion in Structural Biology , v. 20, p. 749-755, 2010.

• ZIDAR, NACE ; TOMAS'IC', TIHOMIR ; S'INK, ROMAN ; RUPNIK, VERONIKA ; KOVAC', ANDREJA ; TURK, SAMO ; PATIN, DELPHINE ; BLANOT, DIDIER ; CONTRERAS MARTEL, CARLOS ; Dessen, Andre'a ; MU'LLER PREMRU, MANICA ; ZEGA, ANAMARIJA ; GOBEC, STANISLAV ; PETERLIN MAS'IC', LUCIJA ; KIKELJ, DANIJEL . Discovery of Novel 5-Benzylidenerhodanine and 5-Benzylidenethiazolidine-2,4-dione Inhibitors of MurD Ligase. Journal of Medicinal Chemistry , v. 53, p. 6584-6594, 2010.

• PLE, S. ; JOB, V. ; Dessen, A. ; ATTREE, I. . Cochaperone Interactions in Export of the Type III Needle Component PscF of Pseudomonas aeruginosa. Journal of Bacteriology (Print) , v. 192, p. 3801-3808, 2010.

• ASCHTGEN, MARIE-STÉPHANIE ; GAVIOLI, MARTHE ; Dessen, Andrea ; LLOUBÈS, ROLAND ; CASCALES, ERIC . The SciZ protein anchors the enteroaggregative Type VI secretion system to the cell wall. Molecular Microbiology (Print) , v. 75, p. 886-899, 2010.

• JOB, V. ; MATTEI, P.-J. ; LEMAIRE, D. ; ATTREE, I. ; Dessen, A. . Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins. Journal of Biological Chemistry (Online) , v. 285, p. 23224-23232, 2010.

• IZORÉ, THIERRY ; CONTRERAS-MARTEL, CARLOS ; EL MORTAJI, LAMYA ; MANZANO, CLOTHILDE ; TERRASSE, RÉMY ; VERNET, THIERRY ; DI GUILMI, ANNE MARIE ; Dessen, Andréa . Structural Basis of Host Cell Recognition by the Pilus Adhesin from Streptococcus pneumoniae. Structure (London) , v. 18, p. 106-115, 2010.

• EL MORTAJI, L. ; TERRASSE, R. ; Dessen, A. ; VERNET, T. ; DI GUILMI, A. M. . Stability and Assembly of Pilus Subunits of Streptococcus pneumoniae. Journal of Biological Chemistry (Online) , v. 285, p. 12405-12415, 2010.

• MANZANO, CLOTHILDE ; IZORE', THIERRY ; JOB, VIVIANA ; DI GUILMI, ANNE MARIE ; Dessen, Andre'a . Sortase Activity Is Controlled by a Flexible Lid in the Pilus Biogenesis Mechanism of Gram-Positive Pathogens. Biochemistry (Easton) , v. 48, p. 10549-10557, 2009.

• NEIERS, FABRICE ; MADHURANTAKAM, CHAITHANYA ; FÄLKER, STEFAN ; MANZANO, CLOTHILDE ; Dessen, Andrea ; NORMARK, STAFFAN ; HENRIQUES-NORMARK, BIRGITTA ; ACHOUR, ADNANE . Two Crystal Structures of Pneumococcal Pilus Sortase C Provide Novel Insights into Catalysis and Substrate Specificity. Journal of Molecular Biology , v. 393, p. 704-716, 2009.

• CONTRERAS-MARTEL, CARLOS ; DAHOUT-GONZALEZ, CÉCILE ; MARTINS, ALEXANDRE DOS SANTOS ; KOTNIK, MIHA ; Dessen, Andréa . PBP Active Site Flexibility as the Key Mechanism for β-Lactam Resistance in Pneumococci. Journal of Molecular Biology , v. 387, p. 899-909, 2009.

• MANZANO, CLOTHILDE ; CONTRERAS-MARTEL, CARLOS ; EL MORTAJI, LAMYA ; IZORÉ, THIERRY ; FENEL, DAPHNA ; VERNET, THIERRY ; SCHOEHN, GUY ; DI GUILMI, ANNE MARIE ; Dessen, Andréa . Sortase-Mediated Pilus Fiber Biogenesis in Streptococcus pneumoniae. Structure (London) , v. 16, p. 1838-1848, 2008.

• HUMLJAN, JAN ; KOTNIK, MIHA ; CONTRERAS-MARTEL, CARLOS ; BLANOT, DIDIER ; URLEB, UROS' ; Dessen, Andre'a ; S'OLMAJER, TOM ; GOBEC, STANISLAV . Novel Naphthalene- -sulfonyl- -glutamic Acid Derivatives as Inhibitors of MurD, a Key Peptidoglycan Biosynthesis Enzyme ,. Journal of Medicinal Chemistry , v. 51, p. 7486-7494, 2008.

• TRINDADE, MELISSA B. ; JOB, VIVIANA ; CONTRERAS-MARTEL, CARLOS ; PELICIC, VLADIMIR ; Dessen, Andréa . Structure of a Widely Conserved Type IV Pilus Biogenesis Factor that Affects the Stability of Secretin Multimers. Journal of Molecular Biology , v. 378, p. 1031-1039, 2008.

• MACHEBOEUF, PAULINE ; LEMAIRE, DAVID ; MARTINS, ALEXANDRE DOS SANTOS ; DIDEBERG, OTTO ; JAMIN, MARC ; Dessen, Andréa . Trapping of an Acyl¿Enzyme Intermediate in a Penicillin-binding Protein (PBP)-catalyzed Reaction. Journal of Molecular Biology , v. 376, p. 405-413, 2008.

• JOB, V. ; CARAPITO, R. ; VERNET, T. ; Dessen, A. ; ZAPUN, A. . Common Alterations in PBP1a from Resistant Streptococcus pneumoniae Decrease Its Reactivity toward  -Lactams: STRUCTURAL INSIGHTS. Journal of Biological Chemistry (Online) , v. 283, p. 4886-4894, 2007.

• MACHEBOEUF, PAULINE ; FISCHER, DELPHINE S ; BROWN, TOM ; ZERVOSEN, ASTRID ; LUXEN, ANDRÉ ; JORIS, BERNARD ; Dessen, Andréa ; SCHOFIELD, CHRISTOPHER J . Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins. Nature Chemical Biology , v. 3, p. 565-569, 2007.

• FAUDRY, ERIC ; JOB, VIVIANA ; Dessen, Andréa ; ATTREE, INA ; FORGE, VINCENT . Type¿III secretion system translocator has a molten globule conformation both in its free and chaperone-bound forms. The FEBS Journal (Print) , v. 274, p. 3601-3610, 2007.

• KOTNIK, MIHA ; HUMLJAN, JAN ; CONTRERAS-MARTEL, CARLOS ; OBLAK, MARKO ; KRISTAN, KATJA ; HERVÉ, MIREILLE ; BLANOT, DIDIER ; URLEB, URO' ; GOBEC, STANISLAV ; Dessen, Andréa ; SOLMAJER, TOM . Structural and Functional Characterization of Enantiomeric Glutamic Acid Derivatives as Potential Transition State Analogue Inhibitors of MurD Ligase. Journal of Molecular Biology , v. 370, p. 107-115, 2007.

• QUINAUD, M. ; PLE, S. ; JOB, V. ; CONTRERAS-MARTEL, C. ; SIMORRE, J.-P. ; ATTREE, I. ; Dessen, A. . Structure of the heterotrimeric complex that regulates type III secretion needle formation. Proceedings of the National Academy of Sciences of the United States of America , v. 104, p. 7803-7808, 2007.

• MACHEBOEUF, PAULINE ; CONTRERAS-MARTEL, CARLOS ; JOB, VIVIANA ; DIDEBERG, OTTO ; DESSEN, ANDRéA . Penicillin Binding Proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiology Reviews (Print) , v. 30, p. 673-691, 2006.

• CONTRERAS-MARTEL, CARLOS ; JOB, VIVIANA ; DI GUILMI, ANNE MARIE ; VERNET, THIERRY ; DIDEBERG, OTTO ; Dessen, Andréa . Crystal Structure of Penicillin-binding Protein 1a (PBP1a) Reveals a Mutational Hotspot Implicated in β-Lactam Resistance in Streptococcus pneumoniae. Journal of Molecular Biology , v. 355, p. 684-696, 2006.

• MACHEBOEUF, PAULINE ; DI GUILMI, ANNE MARIE ; JOB, VIVIANA ; VERNET, T. ; DIDEBERG, OTTO ; Dessen A. . Active site restructuring regulates ligand recognition in class A penicillin-binding proteins. Proceedings of the National Academy of Sciences of the United States of America , v. 102, p. 577-582, 2005.

• MORLOT, C. ; PERNOT, L. ; LE GOUELLEC, A. ; DI GUILMI, A. M. ; VERNET, T. ; DIDEBERG, O. ; Dessen, A. . Crystal Structure of a Peptidoglycan Synthesis Regulatory Factor (PBP3) from Streptococcus pneumoniae. The Journal of Biological Chemistry (Print) , v. 280, p. 15984-15991, 2005.

• QUINAUD, M. ; CHABERT, J. ; FAUDRY, E. ; NEUMANN, E. ; LEMAIRE, D. ; PASTOR, A. ; ELSEN, S. ; DESSEN, A. ; ATTREE, I. . The PscE-PscF-PscG Complex Controls Type III Secretion Needle Biogenesis in Pseudomonas aeruginosa. The Journal of Biological Chemistry (Print) , v. 280, p. 36293-36300, 2005.

• GOURE, J. ; PASTOR, A. ; FAUDRY, E. ; CHABERT, J. ; Dessen, A. ; ATTREE, I. . The V Antigen of Pseudomonas aeruginosa Is Required for Assembly of the Functional PopB/PopD Translocation Pore in Host Cell Membranes. Infection and Immunity (Print) , v. 72, p. 4741-4750, 2004.

• NANAO, MAX H ; TCHERNIUK, SERGEY O ; CHROBOCZEK, JADWIGA ; DIDEBERG, OTTO ; Dessen, Andréa ; BALAKIREV, MAXIM Y . Crystal structure of human otubain 2. EMBO Reports (Print) , v. 5, p. 783-788, 2004.

• PERNOT, L. ; CHESNEL, L. ; LE GOUELLEC, A. ; CROIZE, J. ; VERNET, T. ; DIDEBERG, O. ; Dessen, A. . A PBP2x from a Clinical Isolate of Streptococcus pneumoniae Exhibits an Alternative Mechanism for Reduction of Susceptibility to  -Lactam Antibiotics. The Journal of Biological Chemistry (Print) , v. 279, p. 16463-16470, 2004.

• Dessen, Andréa . A New Catalytic Dyad Regulates Anchoring of Molecules to the Gram-Positive Cell Wall by Sortases. Structure (London) , v. 12, p. 6-7, 2004.

• NANAO, MAX ; RICARD-BLUM, SYLVIE ; DI GUILMI, ANNE ; LEMAIRE, DAVID ; LASCOUX, DAVID ; CHABERT, JACQUELINE ; ATTREE, INA ; Dessen, Andréa . Type III secretion proteins PcrV and PcrG from Pseudomonas aeruginosa form a 1:1 complex through high affinity interactions. BMC Microbiology (Online) , v. 3, p. 21, 2003.

• DI GUILMI, A. M. ; Dessen, A. ; DIDEBERG, O. ; VERNET, T. . The Glycosyltransferase Domain of Penicillin-Binding Protein 2a from Streptococcus pneumoniae Catalyzes the Polymerization of Murein Glycan Chains. Journal of Bacteriology (Print) , v. 185, p. 4418-4423, 2003.

• JOB, VIVIANA ; DI GUILMI, ANNE MARIE ; MARTIN, LYDIE ; VERNET, THIERRY ; DIDEBERG, OTTO ; Dessen, Andréa . Structural studies of the transpeptidase domain of PBP1a from. Acta Crystallographica. Section D, Biological Crystallography , v. 59, p. 1067-1069, 2003.

• GOMIS-RÜTH, F.XAVIER ; Dessen, Andréa ; TIMMINS, JOANNA ; BRACHER, ANDREAS ; KOLESNIKOWA, LARISSA ; BECKER, STEPHAN ; KLENK, HANS-DIETER ; WEISSENHORN, WINFRIED . The Matrix Protein VP40 from Ebola Virus Octamerizes into Pore-like Structures with Specific RNA Binding Properties. Structure (London) , v. 11, p. 423-433, 2003.

• DI GUILMI, A. M. ; Dessen, A. ; DIDEBERG, O. ; VERNET, T. . Functional Characterization of Penicillin-Binding Protein 1b from Streptococcus pneumoniae. Journal of Bacteriology (Print) , v. 185, p. 1650-1658, 2003.

• SCHOEHN, G. ; DI GUILMI, A. M. ; LEMAIRE, D. ; ATTREE, I. ; WEISSENHORN, W. ; DESSEN, A. . Oligomerization of type III secretion proteins PopB and PopD precedes pore formation in Pseudomonas. The EMBO Journal , v. 22, p. 4957-4967, 2003.

• DI GUILMI, ANNE ; Dessen, Andrea ; DIDEBERG, OTTO ; VERNET, THIERRY . Bifunctional Penicillin-Binding Proteins: Focus on the Glycosyltransferase Domain and its Specific Inhibitor Moenomycin. Current Pharmaceutical Biotechnology (Print) , v. 3, p. 63-75, 2002.

• DI GUILMI, A. M. ; DESSEN, A. . New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae. EMBO Reports (Print) , v. 3, p. 728-734, 2002.

• Dessen, A. ; DI GUILMI, A. ; VERNET, T. ; DIDEBERG, O. . Molecular Mechanisms of Antibiotic Resistance in Gram-Positive Pathogens.. Current Drug Targets. Infectious Disorders , v. 1, p. 63-77, 2001.

• DESSEN, A. . Crystal Structure of PBP2x from a Highly Penicillin-resistant Streptococcus pneumoniae Clinical Isolate. A MOSAIC FRAMEWORK CONTAINING 83 MUTATIONS. The Journal of Biological Chemistry (Print) , v. 276, p. 45106-45112, 2001.

• Dessen, Andréa . Structure and mechanism of human cytosolic phospholipase A2. Biochimica and Biophysica Acta. Molecular and Cell Biology of Lipids , v. 1488, p. 40-47, 2000.

• DESSEN, A. . Crystal structure of the matrix protein VP40 from Ebola virus. The EMBO Journal , v. 19, p. 4228-4236, 2000.

• RUIGROK, ROB W.H ; SCHOEHN, GUY ; Dessen, Andréa ; FOREST, ERIC ; VOLCHKOV, VIKTOR ; DOLNIK, OLGA ; KLENK, HANS-DIETER ; WEISSENHORN, WINFRIED . Structural characterization and membrane binding properties of the matrix protein VP40 of ebola virus. Journal of Molecular Biology , v. 300, p. 103-112, 2000.

• Dessen, Andréa ; FOREST, ERIC ; VOLCHKOV, VIKTOR ; DOLNIK, OLGA ; KLENK, HANS-DIETER ; WEISSENHORN, WINFRIED . Crystallization and preliminary X-ray analysis of the matrix protein from Ebola virus. Acta Crystallographica. Section D, Biological Crystallography , v. 56, p. 758-760, 2000.

• DESSEN, A . Phospholipase A2 enzymes: structural diversity in lipid messenger metabolism. Structure (London) , v. 8, p. R15-R22, 2000.

• SOMOZA, JOHN R ; MENON, SAURABH ; SCHMIDT, HOLLY ; JOSEPH-MCCARTHY, DIANE ; Dessen, Andréa ; STAHL, MARK L ; SOMERS, WILLIAM S ; SULLIVAN, FRANCIS X . Structural and kinetic analysis of Escherichia coli GDP-mannose 4,6 dehydratase provides insights into the enzyme-s catalytic mechanism and regulation by GDP-fucose. Structure (London) , v. 8, p. 123-135, 2000.

• Dessen, Andréa ; TANG, JIN ; SCHMIDT, HOLLY ; STAHL, MARK ; CLARK, JAMES D. ; SEEHRA, JASBIR ; SOMERS, WILLIAM S. . Crystal Structure of Human Cytosolic Phospholipase A2 Reveals a Novel Topology and Catalytic Mechanism. Cell (Cambridge) , v. 97, p. 349-360, 1999.

• OLSEN, LAURENCE R. ; Dessen, Andréa ; GUPTA, DIPTI ; SABESAN, SUBRAMANIAM ; SACCHETTINI, JAMES C. ; BREWER, C. FRED . X-ray Crystallographic Studies of Unique Cross-Linked Lattices between Four Isomeric Biantennary Oligosaccharides and Soybean Agglutinin. Biochemistry (Easton) , v. 36, p. 15073-15080, 1997.

• Dessen, Andréa ; LAWRENCE, C.MARTIN ; CUPO, SUSAN ; ZALLER, DENNIS M. ; WILEY, DON C. . X-Ray Crystal Structure of HLA-DR4 (DRA*0101, DRB1*0401) Complexed with a Peptide from Human Collagen II. Immunity (Cambridge, Mass.) , v. 7, p. 473-481, 1997.

• WEISSENHORN, W. ; CALDER, L. J. ; DESSEN, A. ; LAUE, T. ; SKEHEL, J. J. ; WILEY, D. C. . Assembly of a rod-shaped chimera of a trimeric GCN4 zipper and the HIV-1 gp41 ectodomain expressed in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America (Online) , v. 94, p. 6065-6069, 1997.

• WEISSENHORN, W. ; DESSEN, A. ; HARRISON, S. C. ; SKEHEL, J. J. ; WILEY, D. C. . Atomic structure of the ectodomain from HIV-1 gp41. Nature (London) , v. 387, p. 426-430, 1997.

• QUEMARD, ANNAIEK ; SACCHETTINI, JAMES C. ; Dessen, Andrea ; VILCHEZE, CATHERINE ; BITTMAN, ROBERT ; JACOBS, WILLIAM R. ; BLANCHARD, JOHN S. . Enzymic Characterization of the Target for Isoniazid in Mycobacterium tuberculosis. Biochemistry (Easton) , v. 34, p. 8235-8241, 1995.

• Dessen, Andrea ; GUPTA, DIPTI ; SABESAN, SUBRAMANIAM ; BREWER, C. FRED ; SACCHETTINI, JAMES C. . X-ray Crystal Structure of the Soybean Agglutinin Cross-Linked with a Biantennary Analog of the Blood Group I Carbohydrate Antigen. Biochemistry (Easton) , v. 34, p. 4933-4942, 1995.

• DESSEN, A. ; QUEMARD, A. ; BLANCHARD, J. ; JACOBS, W. ; SACCHETTINI, J. . Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis. Science (New York, N.Y.) , v. 267, p. 1638-1641, 1995.

• SCAPIN, GIOVANNA ; SACCHETTINI, JAMES C. ; Dessen, Andrea ; BHATIA, MOHIT ; GRUBMEYER, CHARLES . Primary Structure and Crystallization of Orotate Phosphoribosyltransferase from Salmonella typhimurium. Journal of Molecular Biology , v. 230, p. 1304-1308, 1993.

• HUGHES, K. ; Dessen, A ; GRAY, J.P. ; GRUBMEYER, C. . The Salmonella typhimurium nadC gene: sequence determination by use of Mud-P22 and purification of quinolinate phosphoribosyltransferase. Journal of Bacteriology , v. 175, p. 479, 1993.

• MIYACHIRO, MAYARA M. ; CONTRERAS-MARTEL, CARLOS ; Dessen, Andréa . Penicillin-Binding Proteins (PBPs) and Bacterial Cell Wall Elongation Complexes. Subcellular Biochemistry. 1ed.: Springer International Publishing, 2019, v. , p. 273-289.

Projetos de pesquisa

• 2018 - 2023

  ANTIBIO-BAC - A parede bacteriana como alvo para o desenvolvimento de novos agentes antimicrobianos, Descrição: A resistência aos antibióticos é um problema imperativo global, e o 'vácuo' no desenvolvimento deste tipo de medicamento dos últimos anos permitiu que os principais patógenos humanos se tornassem resistentes a todos antibióticos, incluindo àqueles de 'ultimo recurso'. Esta realidade exige um esforço multidisciplinar na direção da exploração de novas idéias que possam levar ao desenvolvimento de tratamentos que cujos alvos sejam processos bacterianos essenciais. Um dos interesses recentes do meu grupo tem sido a busca por novos antibióticos potenciais através da triagem de bibliotecas de produtos naturais preparadas à partir da biodiversidade brasileira, uma fonte de agentes antimicrobianos inexplorada. Uma campanha de triagem inicial identificou várias amostras capazes de bloquear a ação das Penicillin-Binding Proteins - PBPs, enzimas essenciais para a formação da parede celular bacteriana, e também o crescimento de bactérias em testes microbiológicos. Além disto, graças ao apoio da FAPESP, pudemos caracterizar estruturalmente o primeiro complexo entre uma PBP e uma molécula parceira que participa da elongação da parede celular, o que abriu as portas para uma melhor compreensão deste processo. O projeto ANTIBIO-BAC tem como objetivo expandir estes resultados encorajadores, e inclui experimentos que visam a caracterização de outros complexos envolvidos na biossíntese da parede bacteriana, bem como a ampliação do esforço na identificação de novos produtos naturais inibidores do processo de resistência aos antibióticos. Este é um projeto que terá impacto tanto nas áreas biológicas como nas de saúde pública.. , Situação: Concluído; Natureza: Pesquisa. , Alunos envolvidos: Doutorado: (3) . , Integrantes: Andrea Dessen de Souza e Silva - Coordenador / MARAGNO TRINDADE, DANIEL - Integrante / Daniela Bareto Barbosa Trivella - Integrante / Roberto Berlinck - Integrante / Andre Lima - Integrante.

• 2018 - Atual

  PSEUDO-WALL: Architecture and function of cell wall synthesis complexes of Pseudomonas aeruginosa, Descrição: Pseudomonas aeruginosa is a major causative agent of hospital- and community-acquired infections, calling for the urgent development of new treatments. The bacterial cell wall is the validated target of mainstream antimicrobials, and a major Achilles? heel for microbial survival. This grant builds on a very successful ANR project (ended Oct 2017) in which Partner 1 structurally and functionally characterized a major protein complex involved in bacterial cell wall formation. Here, we will apply knowledge gained and extend this work to characterize the cell wall assemblies of P. aeruginosa using crystallography, electron microscopy, biochemistry, and microbiology techniques. In addition, we will screen for novel inhibitors of PBP interactions using an automated, large-scale X-ray crystallography-based fragment screening approach, which will be validated using cellular assays developed by Partner 2. The two partners involved have collaborated for over 15 years in the study of biology and virulence of P. aeruginosa, a key factor pointing to the strength of the partnership.. , Situação: Em andamento; Natureza: Pesquisa. , Integrantes: Andrea Dessen de Souza e Silva - Coordenador / ATTRÉE, INA - Integrante., Financiador(es): Agence Nationale de la Recherche - Auxílio financeiro.

• 2015 - Atual

  HEMO-PSEUDO: Pseudomonas aeruginosa-induced hemorrhagic pneumonia: deciphering novel virulence strategies, Descrição: Pseudomonas aeruginosa is an important nosocomial pathogen, associated with high mortality rates, in part attributable to high level intrinsic resistance to antibiotics. Our group recently characterized highly virulent P. aeruginosa clinical strains that lack the most recognized virulence factor, the Type III Secretion System and its corresponding toxin substrates. One of these isolates, CLJ1, is virulent in a mouse model of acute pneumonia, leading to lung hemorrhage, septicemia and rapid death; effects that correlate directly with the reported clinical status of the patient. Using a comparative proteomic approach we identified a novel cytolysin named Exolysin. This family of toxins is known to be exported via a two-partner secretion (TPS) system; notably, in P. aeruginosa CLJ1, immediately upstream of exlA (encoding the ?exolysin?), we identified a gene (exlB) encoding its potential cognate TPS partner. Preliminary genome analysis indicated that the CLJ series are related to the taxonomic outlier strain PA7 (www.pseudomonas.com). Recently, we assembled a collection of CLJ1/PA7-like strains originating from different infections and diverse environments. These strains share the core genome with other P. aeruginosa strains, but possess in addition of exlBA, other unique, yet uncharacterized genomic islands that may give them specific adaptation capacities in specific environments. Indeed, it is known that PA7/CLJ isolates can acquire pan-resistance to antibiotics through yet unknown mechanisms, revealed by antibiograms performed after chemotherapy on some highly virulent strains (Elsen et al., 2014). Furthermore, the pathogenic phenotype of the strains was also found to be variable, with some being extremely cytolytic in different cellular models. Therefore, these strains display a YET UNCHARACTERIZED, TOTALLY NOVEL mechanism of pathogenicity. In this project, we will undertake an integrated study of the CLJ P. aeruginosa clinical isolates from microbiological, biochemical, cellular, tissular and structural viewpoints, combined with genome-wide approaches, with the objective of delineating the mechanisms bacterial pathogenesis utilized by these strains. Notably, the study of the Exolysin secretion process, its action on immune/epithelial/endothelial cells, and global host responses to this type of pathogenesis process will be essential for the development of novel anti-virulence strategies. Moreover, the understanding of global changes at transcriptional levels between strains that differ phenotypically should open new paths towards the comprehension of bacterial patho-adaptation processes. Team 1 (coordinator) will study all aspects of bacterial virulence in cellular and animal models. The team members have extensive experience in P. aeruginosa biology, virulence gene regulation and protein secretion. Recently, a mouse model of acute infection was established and will be used to delineate host responses and damages provoked by these hemorrhagic strains. Team 1 will continue an already established collaboration with Steve Lory?s lab at Harvard Medical School analyzing genome evolution and regulatory pathways controlling virulence. Team 2 has a long-term experience and recognized excellence in structural characterization of bacterial virulence factors and cell-wall proteins. The members of the Team will tackle the Exolysin toxin and its partners/targets to decipher their three-dimensional structure and study, with Partner 1, structure-function relationships. The results that will be generated through this project will have great impact not only at the level of a vast scientific community, but also for physicians and hospital staff in charge of controlling bacterial infection. Because of the dramatic impact of Exolysin on cells and tissues, targeting this protein in future antibacterial adjuvant therapy could be of high clinical. , Situação: Em andamento; Natureza: Pesquisa. , Integrantes: Andrea Dessen de Souza e Silva - Integrante / ATTRÉE, INA - Coordenador.

• 2013 - 2017

  BACSCREEN: Assembly and structure of macromolecular complexes involved in bacterial cell wall biosynthesis, Descrição: The bacterial cell wall is a complex three-dimensional structure that protects the cell from environmental stress and ensures its shape. It also plays a key role during the processes of cell division and bacterial cell wall elongation. The biosynthesis of its main building block, the peptidoglycan, involves the coordination of activities of proteins present in both cytoplasmic and periplasmic compartments, some of which also interact with the bacterial cytoskeleton. Although targeting the peptidoglycan biosynthetic pathway with β-lactam antibiotics has been a highly successful strategy to combat bacterial infections for over eighty years, antibiotic resistant strains have been reported worldwide. Notably, the sheer complexity of the cell wall formation process has created a significant challenge for the development of novel antibacterials as well as for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. In the BACSCREEN project, we will structurally and functionally characterize macromolecular complexes involved in both cytoplasmic and periplasmic phases of peptidoglycan biosynthesis. We will tackle the study of a cytoplasmic complex formed by Mur synthetases, proposed to act in ?channeling? of peptidoglycan building blocks towards the membrane, as well as PBP assemblies, involved in the two last enzymatic reactions required for peptidoglycan biosynthesis. We will accomplish these goals through the employment of a combination of X-ray crystallography, small angle scattering (SAXS), electron microscopy, and genetic and microbiological methodologies. In addition, by using a time-resolved fluorescence that is already available to us through a collaboration with Hybrigenics and that detect interactions between PBP and its periplasmic partners, we will screen chemical libraries in the search for inhibitors of such interactions. The availability of preliminary results obtained through the collaboration between the two partners involved, including a fluorescence assay already proven to identify interactions within PBP assemblies, indicates that the work proposed here will succeed in revealing key aspects of peptidoglycan assembly machineries that will be important not only for the drug development field but also for the understanding of general mechanisms of bacterial cell wall synthesis and macromolecular complex formation.. , Situação: Concluído; Natureza: Pesquisa. , Integrantes: Andrea Dessen de Souza e Silva - Coordenador / BONECA, IVO G. - Integrante., Financiador(es): Agence Nationale de la Recherche - Auxílio financeiro.

• 2012 - 2017

  BACWALL - Estruturação de complexos macromoleculares da parede bacteriana: biossíntese e virulência, Descrição: A parede bacteriana e uma estrutura tri-dimensional complexa que protege a célula de diferenças de pressão osmótica, garante a sua forma, e exerce um papel importante no processo de divisão celular. Além disto, é essencial para a ancoragem de fatores de virulência e sistemas de secreção de toxinas, ambos importantes não só para o processo infeccioso mas também para a sobrevivência do microorganismo. O processo de biossíntese da parede bacteriana em si é o alvo dos antibióticos do tipo β-lactamina, que combatem infecções há mais de 80 anos. Porém, a proliferação de cepas resistentes à estas drogas, adicionada ao interesse diminuído da industria farmacêutica pela pesquisa nesta área, exige a organização de um esforço de laboratórios acadêmicos que vise a compreensão de diferentes aspectos da biologia da parede bacteriana, o que eventualmente levará ao desenvolvimento de novos tratamentos contra estas infecções. No projeto BACWALL, nosso objetivo é de caracterizar de maneira estrutural e funcional complexos macromoleculares essenciais para a biossíntese e reparação da parede bacteriana, como os formados pelas Penicillin-Binding Proteins. Além disto, também estudaremos complexos envolvidos no processo de virulência bacteriana que dependem da parede para sua estabilidade e função. Realizaremos estes objetivos utilizando técnicas como a cristalografia de raios-X, bioquímica, biologia molecular, e microscopia eletrônica. A disponibilidade de um número vasto de resultados preliminares sugere que o trabalho proposto aqui revelará detalhes chave das maquinarias de biossíntese da parede bacteriana e de virulência, e os resultados serão importantes não somente para o campo de desenvolvimento de novos antibióticos mas também para a compreensão de mecanismos generalizados de formação de complexos macromoleculares.. , Situação: Concluído; Natureza: Pesquisa. , Alunos envolvidos: Mestrado acadêmico: (1) Doutorado: (3) . , Integrantes: Andrea Dessen de Souza e Silva - Coordenador / Trindade, D. - Integrante.

Prêmios