Inmunología y Microbiología Molecular

Fernando Goldbaum - Fundación Instituto Leloir

idioma:

El objetivo principal de nuestro laboratorio es entender los mecanismos moleculares que subyacen (i) a la patogenicidad bacteriana y (ii) a la respuesta del sistema inmune contra proteínas inmunogénicas. Queremos entender:
  1. Como Brucella y otras bacterias infectivas son capaces de sensar las claves ambientales (tensión de oxígeno, potenciales redox, luz, etc.)?
  2. Cuales de las adaptaciones metabólicas de Brucella son importantes para generar una infección efectiva en el hospedador y como podemos manipularlas para interrumpir el proceso infeccioso?
  3. Como los factores de virulencia de Brucella afectan la interacción hospedador-microbio?
  4. Cuales son las bases moleculares y celulares que explican la inmunogenicidad de la Lumazina Sintasa de Brucella (BLS)?
  5. Podemos crear vacunas terapéuticas y protectivas usando ingeniería de proteínas sobre la estructura de BLS?
 

El carácter multidisciplinario del grupo de trabajo permite abarcar diversos aspectos de los temas de investigación. Uno de los temas de estudio del laboratorio es el metabolismo de flavinas y el rol de flavoproteínas en Brucella y otros Rhizobiales. Descubrimos que algunas enzimas del metabolismo de flavinas constituyen factores de virulencia que actúan en el nicho replicativo de la bacteria, y que Brucella tiene un metabolismo de síntesis de flavinas atípico. Investigamos en forma general el rol de la biosíntesis de flavinas en la adaptación metabólica que sufre este patógeno intracelular en su nicho replicativo pobre en nutrientes y en oxígeno. Nuestra principal pregunta es cómo se adapta Brucella a condiciones de falta de nutrientes y de oxígeno y logra multiplicarse exitosamente, y si las flavinas y flavoproteínas juegan un rol importante en dicha adaptación y en el sensado de señales externas tales como la luz, la tensión de oxígeno y otras. Estudiamos además una flavoproteína de Brucella, LOV-HK, que es capaz de sensar la luz azul y de esa manera modula la virulencia de la bacteria. Por otro lado, estudiamos las características inmunológicas de una proteína polimérica de Brucella, la lumazina sintetasa (BLS) al ser utilizada como carrier vacunal y el rol de receptores de tipo Toll en dicha respuesta. Algunas de las técnicas que se realizan:
  • Mutaciones y deleciones de genes de interés, y complementación de las mismas.
  • Caracterización del la regulación transcripcional y traduccional de los genes de interés.
  • Estudio de la actividad bioquímica de las enzimas de la vía metabólica de las flavinas.
  • Estudio de la actividad bioquímica de las flavoproteínas sensoras y sus mecanismos de transducción de señales.
  • Estudios de estructura/función de proteínas mediante cristalografía de Rayos y RMN.
  • Estudio de interacción proteína-proteína in vitro mediante técnicas biofísicas y display en fagos.
  • Estudio de interacción proteína-proteína in vivo mediante técnicas de doble híbrido bacteriano.
  • Estudios microbiológicos de crecimiento bacteriano.
  • Estudios in vitro en cultivos primarios y líneas celulares.
  • Estudios inmunológicos básicos y de infección en el modelo murino.
  • Utilización de microscopía de fluorescencia y confocal.


2017


The superfamily keeps growing: Identification in trypanosomatids of RibJ, the first riboflavin transporter family in protists.

Balcazar DE, Vanrell MC, Romano PS, Pereira CA, Goldbaum FA, Bonomi HR, Carrillo C.

PLoS Negl Trop Dis. 2017 Apr 13;11(4):e0005513. doi: 10.1371/journal.pntd.0005513. eCollection 2017 Apr.
PMID: 28406895

Characterization of structural and immunological properties of a fusion protein between flagellin from Salmonella and lumazine synthase from Brucella.

Hiriart Y, Rossi AH, Biedma ME, Errea AJ, Moreno G, Cayet D, Rinaldi J, Blancá B, Sirard JC, Goldbaum F, Berguer P, Rumbo M.

Protein Sci. 2017 May;26(5):1049-1059. doi: 10.1002/pro.3151. Epub 2017 Mar 16.
PMID:28257593

Polymeric antigen BLSOmp31 in aluminium hydroxide induces serum bactericidal and opsonic antibodies against Brucella canis in dogs.

Clausse M, Díaz AG, Pardo RP, Zylberman V, Goldbaum FA, Estein SM.

Vet Immunol Immunopathol. 2017 Feb;184:36-41. doi: 10.1016/j.vetimm.2016.11.004. Epub 2016 Dec 5.
PMID: 28166930

Three-Dimensional Structure of Full-Length NtrX, an Unusual Member of the NtrC Family of Response Regulators.

Fernández I, Cornaciu I, Carrica MD, Uchikawa E, Hoffmann G, Sieira R, Márquez JA, Goldbaum FA.

J Mol Biol. 2017 Apr 21;429(8):1192-1212. doi: 10.1016/j.jmb.2016.12.022. Epub 2017 Jan 12.
PMID: 28088479

Structural and functional characterization of a cold adapted TPM-domain with ATPase/ADPase activity.

Cerutti ML, Otero LH, Smal C, Pellizza L, Goldbaum FA, Klinke S, Aran M.

J Struct Biol. 2017 Mar;197(3):201-209. doi: 10.1016/j.jsb.2016.10.010. Epub 2016 Nov 1.
PMID: 27810564

2016


Xanthomonas campestris attenuates virulence by sensing light through a bacteriophytochrome photoreceptor.

Bonomi HR, Toum L, Sycz G, Sieira R, Toscani AM, Gudesblat GE, Leskow FC, Goldbaum FA, Vojnov AA, Malamud F.

EMBO Rep. 2016 Nov;17(11):1565-1577.
PMID: 27621284

Cerutti ML, Otero LH, Smal C, Pellizza L, Goldbaum FA, Klinke S, Aran M.

J Struct Biol. 2016 Nov 1. pii: S1047-8477(16)30230-1. doi: 10.1016/j.jsb.2016.10.010. [Epub ahead of print]

Díaz AG, Quinteros DA, Gutiérrez SE, Rivero MA, Palma SD, Allemandi DA, Pardo RP, Zylberman V, Goldbaum FA, Estein SM.

Vet Immunol Immunopathol. 2016 Oct 1;178:50-6. doi: 10.1016/j.vetimm.2016.07.004.
PMID: 27496742

Development of camelid single chain antibodies against Shiga toxin type 2 (Stx2) with therapeutic potential against Hemolytic Uremic Syndrome (HUS).

Mejías MP, Hiriart Y, Lauché C, Fernández-Brando RJ, Pardo R, Bruballa A, Ramos MV, Goldbaum FA, Palermo MS, Zylberman V.
Sci Rep. 2016 Apr 27;6:24913. doi: 10.1038/srep24913.
PMID:27118524

Structure of the Full-Length Bacteriophytochrome from the Plant Pathogen Xanthomonas campestris Provides Clues to its Long-Range Signaling Mechanism.

Otero LH, Klinke S, Rinaldi J, Velázquez-Escobar F, Mroginski MA, Fernández López M, Malamud F, Vojnov AA, Hildebrandt P, Goldbaum FA, Bonomi HR.
J Mol Biol. 2016 Sep 25;428(19):3702-20. doi: 10.1016/j.jmb.2016.04.012. Epub 2016 Apr 20.
PMID:27107635

Spray dried microspheres based on chitosan: A promising new carrier for intranasal administration of polymeric antigen BLSOmp31 for prevention of ovine brucellosis.

Díaz AG, Quinteros DA, Llabot JM, Palma SD, Allemandi DA, Ghersi G, Zylberman V, Goldbaum FA, Estein SM.
Mater Sci Eng C Mater Biol Appl. 2016 May;62:489-96. doi: 10.1016/j.msec.2016.01.084. Epub 2016 Feb 2.
PMID:26952451

Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

Rinaldi J, Arrar M, Sycz G, Cerutti ML, Berguer PM, Paris G, Estrín DA, Martí MA, Klinke S, Goldbaum FA.
J Mol Biol. 2016 Mar 27;428(6):1165-79. doi: 10.1016/j.jmb.2016.01.026. Epub 2016 Feb 2.
PMID:26851072

2015


Expression of the Multimeric and Highly Immunogenic Brucella spp. Lumazine Synthase Fused to Bovine Rotavirus VP8d as a Scaffold for Antigen Production in Tobacco Chloroplasts.

Alfano EF, Lentz EM, Bellido D, Dus Santos MJ, Goldbaum FA, Wigdorovitz A, Bravo-Almonacid FF.
Front Plant Sci. 2015 Dec 23;6:1170. doi: 10.3389/fpls.2015.01170. eCollection 2015.
PMID:26779198

A bacterial protease inhibitor protects antigens delivered in oral vaccines from digestion while triggering specific mucosal immune responses.

Ibañez AE, Coria LM, Carabajal MV, Delpino MV, Risso GS, Cobiello PG, Rinaldi J, Barrionuevo P, Bruno L, Frank F, Klinke S, Goldbaum FA, Briones G, Giambartolomei GH, Pasquevich KA, Cassataro J.
J Control Release. 2015 Dec 28;220(Pt A):18-28. doi: 10.1016/j.jconrel.2015.10.011. Epub 2015 Oct 9.
PMID:26456256

S-SAD phasing of monoclinic histidine kinase from Brucella abortus combining data from multiple crystals and orientations: an example of data-collection strategy and a posteriori analysis of different data combinations.

Klinke S, Foos N, Rinaldi JJ, Paris G, Goldbaum FA, Legrand P, Guimarães BG, Thompson A.
Acta Crystallogr D Biol Crystallogr. 2015 Jul;71(Pt 7):1433-43. doi: 10.1107/S1399004715007622. Epub 2015 Jun 30.
PMID:26143915

Snapshots of Conformational Changes Shed Light into the NtrX Receiver Domain Signal Transduction Mechanism.

Fernández I, Otero LH, Klinke S, Carrica Mdel C, Goldbaum FA.
J Mol Biol. 2015 Oct 9;427(20):3258-72. doi: 10.1016/j.jmb.2015.06.010. Epub 2015 Jun 23.
PMID:26113057

LOV Histidine Kinase Modulates the General Stress Response System and Affects the virB Operon Expression in Brucella abortus.

Sycz G, Carrica MC, Tseng TS, Bogomolni RA, Briggs WR, Goldbaum FA, Paris G.
PLoS One. 2015 May 19;10(5):e0124058. doi: 10.1371/journal.pone.0124058. eCollection 2015.
PMID:25993430

Brucella spp. Lumazine Synthase Induces a TLR4-Mediated Protective Response against B16 Melanoma in Mice.

Rossi AH, Farias A, Fernández JE, Bonomi HR, Goldbaum FA, Berguer PM.
PLoS One. 2015 May 14;10(5):e0126827. doi: 10.1371/journal.pone.0126827. eCollection 2015.
PMID:25973756

Extensive Identification of Bacterial Riboflavin Transporters and Their Distribution across Bacterial Species.

Gutiérrez-Preciado A, Torres AG, Merino E, Bonomi HR, Goldbaum FA, García-Angulo VA.
PLoS One. 2015 May 4;10(5):e0126124. doi: 10.1371/journal.pone.0126124. eCollection 2015.
PMID:25938806

Selection of nanobodies that block the enzymatic and cytotoxic activities of the binary Clostridium difficile toxin CDT.

Unger M, Eichhoff AM, Schumacher L, Strysio M, Menzel S, Schwan C, Alzogaray V, Zylberman V, Seman M, Brandner J, Rohde H, Zhu K, Haag F, Mittrücker HW, Goldbaum F, Aktories K, Koch-Nolte F.
Sci Rep. 2015 Jan 19;5:7850. doi: 10.1038/srep07850.
PMID:25597743

2014


Crystallization and preliminary X-ray characterization of the full-length bacteriophytochrome from the plant pathogen Xanthomonas campestris pv. campestris.

Klinke S, Otero LH, Rinaldi J, Sosa S, Guimarães BG, Shepard WE, Goldbaum FA, Bonomi HR.
Acta Crystallogr F Struct Biol Commun. 2014 Dec 1;70(Pt 12):1636-9. doi: 10.1107/S2053230X14023243. Epub 2014 Nov 14.
PMID:25484215

Solution and crystal structure of BA42, a protein from the Antarctic bacterium Bizionia argentinensis comprised of a stand-alone TPM domain.

Aran M, Smal C, Pellizza L, Gallo M, Otero LH, Klinke S, Goldbaum FA, Ithurralde ER, Bercovich A, Mac Cormack WP, Turjanski AG, Cicero DO.
Proteins. 2014 Nov;82(11):3062-78. doi: 10.1002/prot.24667. Epub 2014 Sep 3.
PMID:25116514

Crystallographic and kinetic study of riboflavin synthase from Brucella abortus, a chemotherapeutic target with an enhanced intrinsic flexibility.

Serer MI, Bonomi HR, Guimarães BG, Rossi RC, Goldbaum FA, Klinke S.
Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1419-34. doi: 10.1107/S1399004714005161. Epub 2014 Apr 30.
PMID:24816110

Protection of mice against Shiga toxin 2 (Stx2)-associated damage by maternal immunization with a Brucella lumazine synthase-Stx2 B subunit chimera.

Mejias MP, Cabrera G, Fernández-Brando RJ, Baschkier A, Ghersi G, Abrey-Recalde MJ, Miliwebsky E, Meiss R, Goldbaum F, Zylberman V, Rivas M, Palermo MS.
Infect Immun. 2014 Apr;82(4):1491-9. doi: 10.1128/IAI.00027-14. Epub 2014 Jan 13.
PMID:24421050

2013


Identification and characterization of RibN, a novel family of riboflavin transporters from Rhizobium leguminosarum and other proteobacteria.

García Angulo VA, Bonomi HR, Posadas DM, Serer MI, Torres AG, Zorreguieta Á, Goldbaum FA.
J Bacteriol. 2013 Oct;195(20):4611-9. doi: 10.1128/JB.00644-13. Epub 2013 Aug 9.
PMID:23935051

Immunization with a chimera consisting of the B subunit of Shiga toxin type 2 and brucella lumazine synthase confers total protection against Shiga toxins in mice.

Mejias MP, Ghersi G, Craig PO, Panek CA, Bentancor LV, Baschkier A, Goldbaum FA, Zylberman V, Palermo MS.
J Immunol. 2013 Sep 1;191(5):2403-11. doi: 10.4049/jimmunol.1300999. Epub 2013 Aug 5.
PMID:23918978

The vaccine candidate BLSOmp31 protects mice against Brucella canis infection.

Clausse M, Díaz AG, Ghersi G, Zylberman V, Cassataro J, Giambartolomei GH, Goldbaum FA, Estein SM.
Vaccine. 2013 Dec 9;31(51):6129-35. doi: 10.1016/j.vaccine.2013.07.041. Epub 2013 Jul 30.
PMID:23906889

Immune response and serum bactericidal activity against Brucella ovis elicited using a short immunization schedule with the polymeric antigen BLSOmp31 in rams.

Díaz AG, Clausse M, Paolicchi FA, Fiorentino MA, Ghersi G, Zylberman V, Goldbaum FA, Estein SM.
Vet Immunol Immunopathol. 2013 Jul 15;154(1-2):36-41. doi: 10.1016/j.vetimm.2013.04.003. Epub 2013 Apr 11.
PMID:23643287

The art of blocking ADP-ribosyltransferases (ARTs): nanobodies as experimental and therapeutic tools to block mammalian and toxin ARTs.

Menzel S, Rissiek B, Haag F, Goldbaum FA, Koch-Nolte F.
FEBS J. 2013 Aug;280(15):3543-50. doi: 10.1111/febs.12313. Epub 2013 Jun 14. Review.
PMID:23627412

The two-component systems PrrBA and NtrYX co-ordinately regulate the adaptation of Brucella abortus to an oxygen-limited environment.

Carrica Mdel C, Fernandez I, Sieira R, Paris G, Goldbaum FA.
Mol Microbiol. 2013 Apr;88(2):222-33. doi: 10.1111/mmi.12181. Epub 2013 Mar 26.
PMID:23527685

Tandem repeats of the extracellular domain of Matrix 2 influenza protein exposed in Brucella lumazine synthase decameric carrier molecule induce protection in mice.

Alvarez P, Zylberman V, Ghersi G, Boado L, Palacios C, Goldbaum F, Mattion N.
Vaccine. 2013 Jan 21;31(5):806-12. doi: 10.1016/j.vaccine.2012.11.072. Epub 2012 Dec 27.
PMID:23246552

2012


A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants.

Berguer PM, Alzogaray VA, Rossi AH, Mundiñano J, Piazzon I, Goldbaum FA.
PLoS One. 2012;7(9):e45705. doi: 10.1371/journal.pone.0045705. Epub 2012 Sep 24.
PMID:23029192

Light regulates attachment, exopolysaccharide production, and nodulation in Rhizobium leguminosarum through a LOV-histidine kinase photoreceptor.

Bonomi HR, Posadas DM, Paris G, Carrica Mdel C, Frederickson M, Pietrasanta LI, Bogomolni RA, Zorreguieta A, Goldbaum FA.
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12135-40. doi: 10.1073/pnas.1121292109. Epub 2012 Jul 5.
PMID:22773814

The NtrY/X two-component system of Brucella spp. acts as a redox sensor and regulates the expression of nitrogen respiration enzymes.

Carrica Mdel C, Fernandez I, Martí MA, Paris G, Goldbaum FA.
Mol Microbiol. 2012 Jul;85(1):39-50. doi: 10.1111/j.1365-2958.2012.08095.x. Epub 2012 May 30.
PMID:22582926

The β-scaffold of the LOV domain of the Brucella light-activated histidine kinase is a key element for signal transduction.

Rinaldi J, Gallo M, Klinke S, Paris G, Bonomi HR, Bogomolni RA, Cicero DO, Goldbaum FA.
J Mol Biol. 2012 Jun 29;420(1-2):112-27. doi: 10.1016/j.jmb.2012.04.006. Epub 2012 Apr 11.
PMID:22504229

Polymeric Display of Proteins through High Affinity Leucine Zipper Peptide Adaptors.

Craig PO, Alzogaray V, Goldbaum FA.
Biomacromolecules. 2012 Apr 9;13(4):1112-21. doi: 10.1021/bm201875p. Epub 2012 Mar 20.
PMID:22372794

2011


Heterologous prime-boost oral immunization with GK-1 peptide from Taenia crassiceps cysticerci induces protective immunity.

Fragoso G, Esquivel-Guadarrama F, Santana MA, Bobes RJ, Hernández B, Cervantes J, Segura R, Goldbaum FA, Sciutto E, Rosas G.
Clin Vaccine Immunol. 2011 Jul;18(7):1067-76. doi: 10.1128/CVI.05030-11. Epub 2011 May 18.
PMID:21593234

YqiC of Salmonella enterica serovar Typhimurium is a membrane fusogenic protein required for mice colonization.

Carrica MC, Craig PO, García-Angulo VA, Aguirre A, García-Véscovi E, Goldbaum FA, Cravero SL.
BMC Microbiol. 2011 May 9;11:95. doi: 10.1186/1471-2180-11-95.
PMID:21554724

Sensing the dissociation of a polymeric enzyme by means of an engineered intrinsic probe.

Ainciart N, Zylberman V, Craig PO, Nygaard D, Bonomi HR, Cauerhff AA, Goldbaum FA.
Proteins. 2011 Apr;79(4):1079-88. doi: 10.1002/prot.22945. Epub 2011 Jan 18.
PMID:21246631

Single-domain llama antibodies as specific intracellular inhibitors of SpvB, the actin ADP-ribosylating toxin of Salmonella typhimurium.

Alzogaray V, Danquah W, Aguirre A, Urrutia M, Berguer P, García Véscovi E, Haag F, Koch-Nolte F, Goldbaum FA.
FASEB J. 2011 Feb;25(2):526-34. doi: 10.1096/fj.10-162958. Epub 2010 Oct 12.
PMID:20940265

2010


An atypical riboflavin pathway is essential for Brucella abortus virulence.

Bonomi HR, Marchesini MI, Klinke S, Ugalde JE, Zylberman V, Ugalde RA, Comerci DJ, Goldbaum FA.
PLoS One. 2010 Feb 25;5(2):e9435. doi: 10.1371/journal.pone.0009435.
PMID:20195542

Single domain antibodies are specially suited for quantitative determination of gliadins under denaturing conditions.

Doña V, Urrutia M, Bayardo M, Alzogaray V, Goldbaum FA, Chirdo FG.
J Agric Food Chem. 2010 Jan 27;58(2):918-26. doi: 10.1021/jf902973c.
PMID:20039674

2009


The polymeric antigen BLSOmp31 confers protection against Brucella ovis infection in rams.

Estein SM, Fiorentino MA, Paolicchi FA, Clausse M, Manazza J, Cassataro J, Giambartolomei GH, Coria LM, Zylberman V, Fossati CA, Kjeken R, Goldbaum FA.
Vaccine. 2009 Nov 12;27(48):6704-11. doi: 10.1016/j.vaccine.2009.08.097. Epub 2009 Sep 11.
PMID:19748579

Single domain antibodies: promising experimental and therapeutic tools in infection and immunity.

Wesolowski J, Alzogaray V, Reyelt J, Unger M, Juarez K, Urrutia M, Cauerhff A, Danquah W, Rissiek B, Scheuplein F, Schwarz N, Adriouch S, Boyer O, Seman M, Licea A, Serreze DV, Goldbaum FA, Haag F, Koch-Nolte F.
Med Microbiol Immunol. 2009 Aug;198(3):157-74. doi: 10.1007/s00430-009-0116-7. Epub 2009 Jun 16. Review.
PMID:19529959

Brucella spp. lumazine synthase as a bovine rotavirus antigen delivery system.

Bellido D, Craig PO, Mozgovoj MV, Gonzalez DD, Wigdorovitz A, Goldbaum FA, Dus Santos MJ.
Vaccine. 2009 Jan 1;27(1):136-45. doi: 10.1016/j.vaccine.2008.10.018. Epub 2008 Oct 28.
PMID:18973781

2008


Relevance of the diversity among members of the Trypanosoma cruzi trans-sialidase family analyzed with camelids single-domain antibodies.

Ratier L, Urrutia M, Paris G, Zarebski L, Frasch AC, Goldbaum FA.
PLoS One. 2008;3(10):e3524. doi: 10.1371/journal.pone.0003524. Epub 2008 Oct 24.
PMID:18949046

Brucella abortus MFP: a trimeric coiled-coil protein with membrane fusogenic activity.

Carrica Mdel C, Craig PO, Alonso Sdel V, Goldbaum FA, Cravero SL.
Biochemistry. 2008 Aug 5;47(31):8165-75. doi: 10.1021/bi800462y. Epub 2008 Jul 11.
PMID:18616282

Structure of the mature ectodomain of the human receptor-type protein-tyrosine phosphatase IA-2.

Primo ME, Klinke S, Sica MP, Goldbaum FA, Jakoncic J, Poskus E, Ermácora MR.
J Biol Chem. 2008 Feb 22;283(8):4674-81. Epub 2007 Nov 29.
PMID:18048354

2007


Renewed hope for a vaccine against the intestinal adult Taenia solium.

Sciutto E, Rosas G, Cruz-Revilla C, Toledo A, Cervantes J, Hernández M, Hernándezt B, Goldbaum FA, de Aluja AS, Fragoso G, Larralde C.
J Parasitol. 2007 Aug;93(4):824-31. Review.
PMID:17918361

Affinity maturation increases the stability and plasticity of the Fv domain of anti-protein antibodies.

Acierno JP, Braden BC, Klinke S, Goldbaum FA, Cauerhff A.
J Mol Biol. 2007 Nov 16;374(1):130-46. Epub 2007 Sep 11.
PMID:17916365

Structural and kinetic properties of lumazine synthase isoenzymes in the order Rhizobiales.

Klinke S, Zylberman V, Bonomi HR, Haase I, Guimarães BG, Braden BC, Bacher A, Fischer M, Goldbaum FA.
J Mol Biol. 2007 Oct 26;373(3):664-80. Epub 2007 Aug 21.
PMID:17854827

Blue-light-activated histidine kinases: two-component sensors in bacteria.

Swartz TE, Tseng TS, Frederickson MA, Paris G, Comerci DJ, Rajashekara G, Kim JG, Mudgett MB, Splitter GA, Ugalde RA, Goldbaum FA, Briggs WR, Bogomolni RA.
Science. 2007 Aug 24;317(5841):1090-3.
PMID:17717187

A DNA vaccine coding for the chimera BLSOmp31 induced a better degree of protection against B. ovis and a similar degree of protection against B. melitensis than Rev.1 vaccination.

Cassataro J, Pasquevich KA, Estein SM, Laplagne DA, Zwerdling A, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH, Goldbaum FA.
Vaccine. 2007 Aug 10;25(32):5958-67. Epub 2007 Jun 12.
PMID:17600596

Single domain antibodies from llama effectively and specifically block T cell ecto-ADP-ribosyltransferase ART2.2 in vivo.

Koch-Nolte F, Reyelt J, Schössow B, Schwarz N, Scheuplein F, Rothenburg S, Haag F, Alzogaray V, Cauerhff A, Goldbaum FA.
FASEB J. 2007 Nov;21(13):3490-8. Epub 2007 Jun 15.
PMID:17575259

Specific recognition of a DNA immunogen by its elicited antibody.

Sanguineti S, Centeno Crowley JM, Lodeiro Merlo MF, Cerutti ML, Wilson IA, Goldbaum FA, Stanfield RL, de Prat-Gay G.
J Mol Biol. 2007 Jun 29;370(1):183-95. Epub 2007 Apr 24.
PMID:17512945

A recombinant subunit vaccine based on the insertion of 27 amino acids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B. ovis than Rev.1 vaccination.

Cassataro J, Pasquevich KA, Estein SM, Laplagne DA, Velikovsky CA, de la Barrera S, Bowden R, Fossati CA, Giambartolomei GH, Goldbaum FA.
Vaccine. 2007 May 30;25(22):4437-46. Epub 2007 Apr 2.
PMID:17442465

Improvement of the synthetic tri-peptide vaccine (S3Pvac) against porcine Taenia solium cysticercosis in search of a more effective, inexpensive and manageable vaccine.

Sciutto E, Rosas G, Hernández M, Morales J, Cruz-Revilla C, Toledo A, Manoutcharian K, Gevorkian G, Blancas A, Acero G, Hernández B, Cervantes J, Bobes RJ, Goldbaum FA, Huerta M, Diaz-Orea A, Fleury A, de Aluja AS, Cabrera-Ponce JL, Herrera-Estrella L, Fragoso G, Larralde C.
Vaccine. 2007 Feb 9;25(8):1368-78. Epub 2006 Oct 23. Review.
PMID:17188784

2006


Antibody recognition of a flexible epitope at the DNA binding site of the human papillomavirus transcriptional regulator E2.

Cerutti ML, Ferreiro DU, Sanguineti S, Goldbaum FA, de Prat-Gay G.
Biochemistry. 2006 Dec 26;45(51):15520-8.
PMID:17176073

Effective protection against experimental Taenia solium tapeworm infection in hamsters by primo-infection and by vaccination with recombinant or synthetic heterologous antigens.

Cruz-Revilla C, Toledo A, Rosas G, Huerta M, Flores-Perez I, Peña N, Morales J, Cisneros-Quiñones J, Meneses G, Díaz-Orea A, Anciart N, Goldbaum F, Aluja A, Larralde C, Fragoso G, Sciutto E.
J Parasitol. 2006 Aug;92(4):864-7.
PMID:16995407

Evolution of vitamin B2 biosynthesis: 6,7-dimethyl-8-ribityllumazine synthases of Brucella.

Zylberman V, Klinke S, Haase I, Bacher A, Fischer M, Goldbaum FA.
J Bacteriol. 2006 Sep;188(17):6135-42.
PMID:16923880

Brucella spp. lumazine synthase: a novel adjuvant and antigen delivery system to effectively induce oral immunity.

Rosas G, Fragoso G, Ainciart N, Esquivel-Guadarrama F, Santana A, Bobes RJ, Ramírez-Pliego O, Toledo A, Cruz-Revilla C, Meneses G, Berguer P, Goldbaum FA, Sciutto E.
Microbes Infect. 2006 Apr;8(5):1277-86. Epub 2006 Feb 7.
PMID:16697684

Exploring protein interfaces with a general photochemical reagent.

Gómez GE, Cauerhff A, Craig PO, Goldbaum FA, Delfino JM. Protein Sci. 2006 Apr;15(4):744-52. PMID:16600965

Brucella outer membrane protein Omp31 is a haemin-binding protein.

Delpino MV, Cassataro J, Fossati CA, Goldbaum FA, Baldi PC.
Microbes Infect. 2006 Apr;8(5):1203-8. Epub 2006 Jan 19.
PMID:16517201

A polymeric bacterial protein activates dendritic cells via TLR4.

Berguer PM, Mundiñano J, Piazzon I, Goldbaum FA.
J Immunol. 2006 Feb 15;176(4):2366-72.
PMID:16455994

2005-2000


Multiple display of a protein domain on a bacterial polymeric scaffold.

Craig PO, Berguer PM, Ainciart N, Zylberman V, Thomas MG, Martinez Tosar LJ, Bulloj A, Boccaccio GL, Goldbaum FA.
Proteins. 2005 Dec 1;61(4):1089-100.
PMID:16193482

Crystallographic studies on decameric Brucella spp. Lumazine synthase: a novel quaternary arrangement evolved for a new function?

Klinke S, Zylberman V, Vega DR, Guimarães BG, Braden BC, Goldbaum FA.
J Mol Biol. 2005 Oct 14;353(1):124-37.
PMID:16165152

Llama single domain antibodies as a tool for molecular mimicry.

Zarebski LM, Urrutia M, Goldbaum FA.
J Mol Biol. 2005 Jun 17;349(4):814-24. Epub 2005 Apr 21.
PMID:15890359

Brucella spp. lumazine synthase: a novel antigen delivery system.

Sciutto E, Toledo A, Cruz C, Rosas G, Meneses G, Laplagne D, Ainciart N, Cervantes J, Fragoso G, Goldbaum FA.
Vaccine. 2005 Apr 15;23(21):2784-90.
PMID:15780726

A viral DNA-binding domain elicits anti-DNA antibodies of different specificities.

Cerutti ML, Zarebski LM, de Prat Gay G, Goldbaum FA.
Mol Immunol. 2005 Feb;42(3):327-33.
PMID:15589321

Engineering of a polymeric bacterial protein as a scaffold for the multiple display of peptides.

Laplagne DA, Zylberman V, Ainciart N, Steward MW, Sciutto E, Fossati CA, Goldbaum FA.
Proteins. 2004 Dec 1;57(4):820-8.
PMID:15390265

Structural mechanism for affinity maturation of an anti-lysozyme antibody.

Cauerhff A, Goldbaum FA, Braden BC.
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3539-44. Epub 2004 Feb 26.
PMID:14988501

High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase.

Zylberman V, Craig PO, Klinke S, Braden BC, Cauerhff A, Goldbaum FA.
J Biol Chem. 2004 Feb 27;279(9):8093-101. Epub 2003 Dec 1.
PMID:14660615

Sequence determinants of quaternary structure in lumazine synthase.

Fornasari MS, Laplagne DA, Frankel N, Cauerhff AA, Goldbaum FA, Echave J.
Mol Biol Evol. 2004 Jan;21(1):97-107. Epub 2003 Oct 1.
PMID:14523158

Brucella lumazine synthase elicits a mixed Th1-Th2 immune response and reduces infection in mice challenged with Brucella abortus 544 independently of the adjuvant formulation used.

Velikovsky CA, Goldbaum FA, Cassataro J, Estein S, Bowden RA, Bruno L, Fossati CA, Giambartolomei GH.
Infect Immun. 2003 Oct;71(10):5750-5.
PMID:14500496

Specific antibody-DNA interaction: a novel strategy for tight DNA recognition.

Di Pietro SM, Centeno JM, Cerutti ML, Lodeiro MF, Ferreiro DU, Alonso LG, Schwarz FP, Goldbaum FA, de Prat-Gay G.
Biochemistry. 2003 May 27;42(20):6218-27.
PMID:12755625

Antibody response to a viral transcriptional regulator.

Cerutti ML, Centeno JM, de Prat-Gay G, Goldbaum FA.
FEBS Lett. 2003 Jan 16;534(1-3):202-6.
PMID:12527387

New approaches to improve a peptide vaccine against porcine Taenia solium cysticercosis.

Sciutto E, Fragoso G, Manoutcharian K, Gevorkian G, Rosas-Salgado G, Hernández-Gonzalez M, Herrera-Estrella L, Cabrera-Ponce J, López-Casillas F, González-Bonilla C, Santiago-Machuca A, Ruíz-Pérez F, Sánchez J, Goldbaum F, Aluja A, Larralde C.
Arch Med Res. 2002 Jul-Aug;33(4):371-8. Review.
PMID:12234527

A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice.

Velikovsky CA, Cassataro J, Giambartolomei GH, Goldbaum FA, Estein S, Bowden RA, Bruno L, Fossati CA, Spitz M.
Infect Immun. 2002 May;70(5):2507-11.
PMID:11953389

Generation of sequence-specific, high affinity anti-DNA antibodies.

Cerutti ML, Centeno JM, Goldbaum FA, de Prat-Gay G.
J Biol Chem. 2001 Apr 20;276(16):12769-73. Epub 2001 Jan 22.
PMID:11279040

Distinctive cognate sequence discrimination, bound DNA conformation, and binding modes in the E2 C-terminal domains from prototype human and bovine papillomaviruses.

Ferreiro DU, Lima LM, Nadra AD, Alonso LG, Goldbaum FA, de Prat-Gay G.
Biochemistry. 2000 Nov 28;39(47):14692-701.
PMID:11087426

Three-dimensional structure of the Fab from a human IgM cold agglutinin.

Cauerhff A, Braden BC, Carvalho JG, Aparicio R, Polikarpov I, Leoni J, Goldbaum FA.
J Immunol. 2000 Dec 1;165(11):6422-8.
PMID:11086081

X-ray crystal structure of an anti-Buckminsterfullerene antibody fab fragment: biomolecular recognition of C(60).

Braden BC, Goldbaum FA, Chen BX, Kirschner AN, Wilson SR, Erlanger BF.
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12193-7.
PMID:11035793

Structural, functional and immunological studies on a polymeric bacterial protein.

Baldi PC, Velikovsky CA, Braden BC, Giambartolomei GH, Fossati CA, Goldbaum FA.
Braz J Med Biol Res. 2000 Jul;33(7):741-7.
PMID:10881048

Divergence in macromolecular assembly: X-ray crystallographic structure analysis of lumazine synthase from Brucella abortus.

Braden BC, Velikovsky CA, Cauerhff AA, Polikarpov I, Goldbaum FA.
J Mol Biol. 2000 Apr 14;297(5):1031-6.
PMID:10764570

1999-1991


[Determination of antiprotein antibodies for the diagnosis of brucellosis in animals].

Baldi PC, Goldbaum FA, Velikovsky CA, Wallach JC, Fossati CA.
Rev Argent Microbiol. 1999;31 Suppl 1:49-51. Review. Spanish. No abstract available.
PMID:10509413

[Diagnosis and progress analysis of human brucellosis via new serological methods].

Wallach JC, Baldi PC, Goldbaum FA, Velikovsky CA, Fossati CA.
Rev Argent Microbiol. 1999;31 Suppl 1:46-8. Review. Spanish. No abstract available.
PMID:10509412

The 18-kDa cytoplasmic protein of Brucella species --an antigen useful for diagnosis--is a lumazine synthase.

Goldbaum FA, Velikovsky CA, Baldi PC, Mörtl S, Bacher A, Fossati CA.
J Med Microbiol. 1999 Sep;48(9):833-9.
PMID:10482294

Lack of significant differences in association rates and affinities of antibodies from short-term and long-term responses to hen egg lysozyme.

Goldbaum FA, Cauerhff A, Velikovsky CA, Llera AS, Riottot MM, Poljak RJ.
J Immunol. 1999 May 15;162(10):6040-5.
PMID:10229844

Crystallization and preliminary x-ray diffraction analysis of the lumazine synthase from Brucella abortus.

Goldbaum FA, Polikarpov I, Cauerhff AA, Velikovsky CA, Braden BC, Poljak RJ.
J Struct Biol. 1998 Oct;123(2):175-8.
PMID:9843672

Characterization of anti-anti-idiotypic antibodies that bind antigen and an anti-idiotype.

Goldbaum FA, Velikovsky CA, Dall'Acqua W, Fossati CA, Fields BA, Braden BC, Poljak RJ, Mariuzza RA.
Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8697-701.
PMID:9238040

Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.

Fields BA, Goldbaum FA, Dall'Acqua W, Malchiodi EL, Cauerhff A, Schwarz FP, Ysern X, Poljak RJ, Mariuzza RA.
Biochemistry. 1996 Dec 3;35(48):15494-503.
PMID:8952503

Crystal structure of an Fv-Fv idiotope-anti-idiotope complex at 1.9 A resolution.

Braden BC, Fields BA, Ysern X, Dall'Acqua W, Goldbaum FA, Poljak RJ, Mariuzza RA.
J Mol Biol. 1996 Nov 22;264(1):137-51.
PMID:8950273

Humoral immune response against lipopolysaccharide and cytoplasmic proteins of Brucella abortus in cattle vaccinated with B. abortus S19 or experimentally infected with Yersinia enterocolitica serotype 0:9.

Baldi PC, Giambartolomei GH, Goldbaum FA, Abdón LF, Velikovsky CA, Kittelberger R, Fossati CA.
Clin Diagn Lab Immunol. 1996 Jul;3(4):472-6.
PMID:8807216

Crystal structure of the complex of the variable domain of antibody D1.3 and turkey egg white lysozyme: a novel conformational change in antibody CDR-L3 selects for antigen.

Braden BC, Fields BA, Ysern X, Goldbaum FA, Dall'Acqua W, Schwarz FP, Poljak RJ, Mariuzza RA.
J Mol Biol. 1996 Apr 19;257(5):889-94.
PMID:8632472

The effect of water activity on the association constant and the enthalpy of reaction between lysozyme and the specific antibodies D1.3 and D44.1.

Goldbaum FA, Schwarz FP, Eisenstein E, Cauerhff A, Mariuzza RA, Poljak RJ.
J Mol Recognit. 1996 Jan-Feb;9(1):6-12.
PMID:8723314

Structure and thermodynamics of antigen recognition by antibodies.

Braden BC, Cauerhff A, Dall'Acqua W, Fields BA, Goldbaum FA, Malchiodi EL, Mariuzza RA, Poljak RJ, Schwarz FP, Ysern X, et al.
Ann N Y Acad Sci. 1995 Sep 29;764:315-27. No abstract available.
PMID:7486542

Molecular basis of antigen mimicry by an anti-idiotope.

Fields BA, Goldbaum FA, Ysern X, Poljak RJ, Mariuzza RA.
Nature. 1995 Apr 20;374(6524):739-42.
PMID:7536303

Thermodynamics of antigen-antibody binding using specific anti-lysozyme antibodies.

Schwarz FP, Tello D, Goldbaum FA, Mariuzza RA, Poljak RJ.
Eur J Biochem. 1995 Mar 1;228(2):388-94.
PMID:7705353

Protein motion and lock and key complementarity in antigen-antibody reactions.

Braden BC, Dall'Acqua W, Eisenstein E, Fields BA, Goldbaum FA, Malchiodi EL, Mariuzza RA, Schwarz FP, Ysern X, Poljak RJ.
Pharm Acta Helv. 1995 Mar;69(4):225-30. Review.
PMID:7651966

Crystallization and preliminary X-ray diffraction study of an idiotope-anti-idiotope Fv-Fv complex.

Goldbaum FA, Fields BA, Cauerhff A, Ysern X, Houdusse A, Eisele JL, Poljak RJ, Mariuzza RA.
J Mol Biol. 1994 Sep 2;241(5):739-43.
PMID:8071997

Solvent rearrangement in an antigen-antibody interface introduced by site-directed mutagenesis of the antibody combining site.

Ysern X, Fields BA, Bhat TN, Goldbaum FA, Dall'Acqua W, Schwarz FP, Poljak RJ, Mariuzza RA.
J Mol Biol. 1994 May 13;238(4):496-500.
PMID:8176740

Structural and physicochemical analysis of the reaction between the anti-lysozyme antibody D1.3 and the anti-idiotopic antibodies E225 and E5.2.

Tello D, Eisenstein E, Schwarz FP, Goldbaum FA, Fields BA, Mariuzza RA, Poljak RJ.
J Mol Recognit. 1994 Mar;7(1):57-62.
PMID:7986568

Removal of LPS from a Brucella cytoplasmic fraction by affinity chromatography with an anti-LPS monoclonal antibody as immunosorbent.

Goldbaum FA, Rubbi CP, Fossati CA.
J Med Microbiol. 1994 Mar;40(3):174-8.
PMID:7509415

Urban outbreak of a Brucella melitensis infection in an Argentine family: clinical and diagnostic aspects.

Wallach JC, Miguel SE, Baldi PC, Guarnera E, Goldbaum FA, Fossati CA.
FEMS Immunol Med Microbiol. 1994 Jan;8(1):49-56.
PMID:8156050

Three-dimensional structure and thermodynamics of antigen binding by anti-lysozyme antibodies.

Tello D, Goldbaum FA, Mariuzza RA, Ysern X, Schwarz FP, Poljak RJ.
Biochem Soc Trans. 1993 Nov;21(4):943-6. No abstract available.
PMID:8132099

Characterization of an 18-kilodalton Brucella cytoplasmic protein which appears to be a serological marker of active infection of both human and bovine brucellosis.

Goldbaum FA, Leoni J, Wallach JC, Fossati CA.
J Clin Microbiol. 1993 Aug;31(8):2141-5.
PMID:8370742

Differentiation between active and inactive human brucellosis by measuring antiprotein humoral immune responses.

Goldbaum FA, Rubbi CP, Wallach JC, Miguel SE, Baldi PC, Fossati CA.
J Clin Microbiol. 1992 Mar;30(3):604-7.
PMID:1551977

Human brucellosis: immunoblotting analysis of three Brucella abortus antigenic fractions allows the detection of components of diagnostic importance.

Goldbaum FA, Morelli L, Wallach J, Rubbi CP, Fossati CA.
Medicina (B Aires). 1991;51(3):227-32.
PMID:1726568

 





Dr. Fernando A. Goldbaum
Investigador Superior - CONICET - fgoldbaum@leloir.org.ar
Scientific Report



Dra. Paula M. Berguer
Investigadora Adjunta - CONICET - pberguer@leloir.org.ar
Scientific Report



Dr. Sebastián Klinke
Investigador Adjunto - CONICET - sklinke@leloir.org.ar
Scientific Report



Dra. María Laura Cerutti
Investigadora Adjunta - CONICET - mcerutti@leloir.org.ar
Scientific Report



Dr. Hernán R. Bonomi
Investigador Adjunto - CONICET - hbonomi@leloir.org.ar



Dr. Lisandro Otero
Investigador Adjunto - CONICET - lotero@leloir.org.ar
Scientific Report



Dra. Jimena J. Rinaldi
Investigadora Asistente - CONICET - jrinaldi@leloir.org.ar
Scientific Report



Dra. Vanina Alzogaray
Investigador Asistente - CONICET - valzogaray@leloir.org.ar
Scientific Report



Lic. Santiago Sosa
Becaria Doctoral - CONICET - ssosa@leloir.org.ar
Scientific Report



Lic. Ana Farias
Becaria Doctoral - CONICET - afarias@leloir.org.ar
Scientific Report



Giuliano T. Antelo
Pasante - gantelo@leloir.org.ar
Scientific Report