ONE HEALTH / Communicable diseases / Bacterial

Laboratory of biophysics and biochemistry of bacterial toxins

● Study of the structure-function of bacterial toxins in different cell types (erythrocytes, platelets, endothelial cells, Caco cells).

● Biomedical applications with toxins (design of detection kits, development of nanosponges for treatment, and immunotoxins).

Work team

Principal Investigator

Herlax, Vanesa

Investigator
vherlax@med.unlp.edu.ar

Pucci Molineris, Melisa

Investigator
mpucci@med.unlp.edu.ar

Pérez Vázquez, Kenia

Research Fellow

kperezvazquez@med.unlp.edu.ar

Collaborators from other institutions

Guzmán, Fanny
Núcleo de Biotecnología Curauma (NBC), Pontificia Universidad Católica de Valparaíso (PUCV), Chile.

Moure-Chanteloup, Isabelle
Institut National de la Transfusion Sanguine, Université Paris Diderot, Paris, France.

Ostuni, Mariano
Institut National de la Transfusion Sanguine, Université Paris Diderot, Paris, France.

Dántola, Laura
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA-La Plata), La Plata. Prov. de Buenos Aires. Argentina.

Maté, Sabina
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), La Plata. Prov. de Buenos Aires. Argentina.

Farina, Mariana
Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Ciudad Autónoma de Buenos Aires Argentina.

García Véscovi, Eleonora
Instituto de Biología Molecular y Celular de Rosario (IBR/CCT-CONICET Rosario, UNR).

Pallarola, Diego
Instituto de Nanosistemas - Universidad Nacional de San Martín (UNSAM), San Martín, Prov. de Buenos Aires. Argentina.

Schwarzbaum, Pablo
Instituto de Química y Fisicoquímica Biológica, Facultad de Farmacia y Bioquímica (INQUIFIB), UBA. Ciudad Autónoma de Buenos Aires, Argentina.

Thomas, Andrés
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA-La Plata), La Plata. Prov. de Buenos Aires. Argentina.

Line overview

In Argentina Escherichia coli causes 75% to 90% of urinary infection episodes, prevailing in neonatal and pediatric urinary infections, in uncomplicated or recurrent cystitis of fertile women as well as in pyelonephritis. These strains are called uropathogenic E. coli (UPEC). Their capacity to invade and colonize other tissues is determined by a set of factors that includes: adherence factors, toxins, iron acquisition systems (siderophores) and capsular antigens. Within toxins these strains secrete, alpha hemolysin and cytotoxic necrotizing factor (CNF-1) are found. Both have shown high correlation with septicemia and kidney failure. In our laboratory we are mainly focused on the study of the alpha hemolysin toxin (HlyA).

The sub-lines of work are as follows:

1-Study of the structure and function of the toxin in different cellular types (erythrocytes, platelets, endothelial cells, Caco cells) in both lithic and sublithic concentrations.

2-Study of the structure-function relationship of HlyA with membrane model systems (liposomes, supported bilayers, monolayers).

3-Interaction of HlyA with chorioamniotic membranes: Model of urinary infection in pregnant women.

4-Rapid kit design for HlyA detection in the urine of patients with urinary infection.

5-Immunotoxin design from peptides of the toxin.

6-Nanosponge design for bacteremia treatment.

Induction of human-fetal-membrane remodeling in-vitro by the alpha hemolysin of Escherichia coli.
Pucci Molineris, M; Schibert, F; Lima, M; Accialini, P; Cané, L; Pelinsky, P; Farina, M; Herlax, V.
2024. Placenta. Mar 25;148:59-68
DOI.org/10.1016/j.placenta.2024.02.001

Alpha hemolysin of Escherichia coli induces a necrotic-like procoagulant state in platelets.
Vázquez, K. P; Tau, J: Denis, M. F. L; Fade,r C. M; Ostuni, M. A; Schwarzbaum, P. J; Herlax, V.
2024. Biochimie. Jun 8:S0300-9084(24)00137-8.
DOI.org/10.1016/j.biochi.2024.06.001

Alpha hemolysin of E. coli induces hemolysis of human erythrocytes independently of toxin interaction with membrane proteins.
Cané. L; Saffioti, N. A; Genetet, S; Daza Millone, M. A; Ostuni, M. A; Schwarzbaum, P. J; Mouro-Chanteloup, I; Herlax, V.
2024. Biochimie. Jan;216:3-13
DOI:10.1016/j.biochi.2023.10.008

Biophysical Analysis to Assess the Interaction of CRAC and CARC Motif Peptides of Alpha Hemolysin of Escherichia coli with Membranes.
Cané, L; Guzmán, F; Balatti, G; Daza Millone, M. A; Pucci Molineris, M; Maté, S; Martini, M. F; Herlax, V.
2023. Biochemistry. Jun 20;62(12):1994-2011
DOI: 10.1021/acs.biochem.3c00164

Interactive Dynamics of Cell Volume and Cell Death in Human Erythrocytes Exposed to α-Hemolysin from Escherichia coli.
Saffioti, Nicolas A.; Lauri, Natalia; Cané, Lucia; Gonzalez-Lebrero, Rodolfo; Alleva, Karina; Mouro-Chanteloup, Isabelle; Ostuni, Mariano A.; Herlax, Vanesa; Schwarzbaum, Pablo Julio.
2022. International journal of molecular sciences. MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI. vol. 23, n° 2, ISSN 1422-0067
DOI: 10.3390/ijms23020872

Extracellular ATP hydrolysis in Caco-2 human intestinal cell line.
Schachter, J.; Alvarez, C.L.; Bazzi, Z.; Faillace, M.P.; Corradi, G.; Hattab, C.; Rinaldi, D.E.; Gonzalez Lebrero, R.; Molineris, M. Pucci; Sévigny, J.; Ostuni, M.A.; Schwarzbaum, P.J.
2021. Biochimica et biophysica acta-biomembranes. : ELSEVIER SCIENCE BV,- . vol. 1863, n° 10, ISSN 0005-2736

Anandamide Exerts a Differential Effect on Human Placenta Before and After the Onset of Labor.
Accialini, Paula; Abán, Cyntia; Etcheverry, Tomás; Negri Malbrán, Mercedes; Leguizamón, Gustavo; Herlax, Vanesa; Maté, Sabina; Farina, Mariana.
2021. Frontiers in physiology. Frontiers Media S. A. vol. 12, ISSN 1664-042X

Role of Tryptophan Residues in the Toxicity and Photosensitized Inactivation of Escherichia coli α-Hemolysin.
Reid, Lara O; Thomas, Andrés H; Herlax, Vanesa; Dántola, M. Laura.
2020. Biochemistry. Washington: AMER CHEMICAL SOC - vol. 59, n° 44, p. 4213-4224. ISSN 0006-2960
doi.org/10.1021/acs.biochem.0c00660

Regulation of extracellular ATP of human erythrocytes treated with α-hemolysin. Effects of cell volume, morphology, rheology and hemolysis.
Leal Denis, M. F.; Lefevre, S. D.; Alvarez, C. L.; Lauri, N.; Enrique, N.; Rinaldi, D.E.; González-Lebrero, R.; Vecchio, L.E.; Espelt, M. V.; Stringa, P.; Muñoz-Garay, C.; Milesi, V.; Ostuni, M. A.; Herlax, V.; Schwarzbaum, P. J.
2019: Biochimica et biophysica acta-molecular cell research. Amsterdam: ELSEVIER SCIENCE BV, vol. 1866, n° 5, p. 896-915. ISSN 0167-4889
doi.org/10.1016/j.bbamcr.2019.01.018

ATPe dynamics in protozoan parasites.
Lauri, Natalia; Bazzi, Zaher; Alvarez, Cora L.; Leal Denis, María F.; Schachter, Julieta; Herlax, Vanesa; Ostuni, Mariano A.; Schwarzbaum, Pablo J.
2019: Adapt or perish. Genes. Basel: MDPI AG, vol. 10, n° 1,
doi.org/10.3390/genes10010016

Induction of erythrocyte microvesicles by Escherichia coli alpha hemolysin.
Strack, Karen; Lauri, Natalia; Maté, Sabina María; Saralegui, Andrés; Muñoz-Garay, Carlos; Schwarzbaum, Pablo J.; Herlax, Vanesa.
2019: Biochemical journal. PORTLAND PRESS LTD, vol. 476, n°22, p. 3455-3473. ISSN 0264-6021
doi.org/10.1042/BCJ20190546

Study of rabbit erythrocytes membrane solubilization by sucrose monomyristate using laurdan and phasor analysis.
Günther, G; Herlax, V; Lillo, M. P; Sandoval-Altamirano, C; Belmar, L. N; Sánchez, S.
2018. Colloids and surfaces b-biointerfaces. ELSEVIER SCIENCE BV, vol. 161, p. 375-385. ISSN 0927-7765

Dynamic regulation of extracellular ATP in Escherichia coli.
Álvarez, C. L; Corradi, G; Lauri, N; Marginedas-Freixa, I; Denis, M. F. L; Enrique, N; Mate, S. M; Milesi, V; Ostuni, M. A; Herlax, V; Schwarzbaum, P. J.
2017. Biochemical journal. England: PORTLAND PRESS LTD. vol. 474, n° 8, p. 1395-1416. ISSN 0264-6021

Interaction of acylated and unacylated forms of E. coli alpha-hemolysin with lipid monolayers: a PM-IRRAS study.
Vázquez, R. F; Daza Millone, M. A; Pavinatto, F. J; Herlax, V. S; Bakás, L. S; Oliveira Jr, O. N; Vela, M. E; Maté, S. M.
2017. Colloids and surfaces b-biointerfaces. Amsterdam: ELSEVIER SCIENCE BV. vol. 158, p. 76-83. ISSN 0927-7765

Microvesicles release and micellar attack as the alternative mechanisms involved in red blood cell membrane solubilization induced by arginine-based surfactants.
Fait, M. E; Hermet, M; Comelles, F; Clapés, P; Álvarez, A; Prieto, E; Herlax, V; Morcelle, S. R; Bakás, L.
2017. Rsc advances. Londres: Royal Chemistry Society. vol. 2017, n° 7, p. 37549-37558

Relationship between intracellular calcium and morphologic changes in rabbit erythrocytes: Effects of the acylated and unacylated forms of E. coli alpha-hemolysin.
Vazquez, R; Mate, S; Bakas, L; Garcia Muñoz, C; Herlax, V.
2016. Biochimica et biophysica acta-biomembranes, Amsterdam: ELSEVIER SCIENCE BV, vol. 1858, n° 8, p. 1944-1953. ISSN 0005-2736

The unfavorable lipid environment reduced caveolin-1 expression in apical membranes from humanpreeclamptic placentas.
Levi, L; Castro Parodi, M; Martínez, N; Piehl, L; Rubín De Celis, E; Herlax, V; Mate, S; Farina, M; Damiano, A. E.
2016. Biochimica et Biophysica Acta-Biomembranes. Amsterdam: ELSEVIER SCIENCE BV, vol. 1858, n° 9, p. 2171-2180. ISSN 0005-2736

Induction of eryptosis by low concentrations of E. coli alpha-hemolysin.
Carrizo, F; Maté, S; Bakás, L; Herlax, V.
2015. Biochimica et Biophysica Acta-Biomembranes. Amsterdam: ELSEVIER SCIENCE BV, vol. 1848, p. 2779-2788. ISSN 0005-2736

Boundary region between coexisting lipid phases as initial binding sites for Escherichia coli alpha-hemolysin: a real-time study.
Maté, S; Vázquez, R; Herlax, V; Daza-Millone, M, A; Fanani, M. L; Maggio, B; Vela, M. E; Bakás, L.
2014. Biochimica et Biophysica acta-Biomembranes: ELSEVIER SCIENCE BV, vol. 1838, p. 1832-1841. ISSN 0005-2736

N-nervonoylsphingomyelin (c24:1) prevents lateral heterogeneity in cholesterol-containing membranes.
Maté, S; Busto, J; García-Arribas, A; Sot, J; Vázquez, R; Herlax, V; Wolf, C; Bakás, L; Goñi, F. M.
2014. Biophysical Journal. United States: CELL PRESS,. vol. 106, p. 2606-2616. ISSN 0006-3495

Novel evidence for the specific interaction between cholesterol and alpha- haemolysin of Escherichia coli.
Vázquez, R. F; Maté, S. M; Bakás, L, S; Fernández, M. M; Malchiodi, E. L; Herlax, V. S.
2014. Biochemical Journal. Londres: PORTLAND PRESS LTD,. vol. 458, n° 3, p. 481-489. ISSN 0264-6021

Mecanismo de acción de la toxina alfa hemolisina de Escherichia coli.
Bakás, L; Maté, S; Vazquez, R; Herlax, V.
2013. Acta bioquímica clínica latinoamericana. La Plata: Federacion Bioquimica Provincia Buenos Aires. vol. 47, n° 2, p. 353-361. ISSN 0325-2957

Mecanismo de acción de la toxina alfa hemolisina de Escherichia coli.
Bakás, L; Maté, S; Vazquez, R; Herlax, V.
2013. Acta bioquímica clínica latinoamericana. La Plata: Federacion Bioquimica Provincia Buenos Aires. vol. 47, n° 2, p. 353-361. ISSN 0325-2957

Contribution of the C-terminal end of apolipoprotein AI to neutralization of lipopolysaccharide endotoxic effect.
Henning, M, F; Herlax, V;Bakas, L.
2011. Innate Immunity 17 (3): 327 - 337

Alpha hemolysin induces and increases of erythrocytes Calcium: A FLIM 2.Photon Phasor Analysis Approach.
Sánchez, S; Bakas, L; Graton, E; Herlax V.
2011. PLos One 2011, 6 (6) e21127. Editorial: PLos One.

Eriptrosis, la muerte suicida de eritrocitos: mecanismo y enfermedades asociadas.
Herlax, V; Vázquez, R; Mate, S; Bakas, L.
2011. Acta Bioquimica Clinica Latinoamericana Actualización45 (2): 287-96. Editorial: Publicación de Federación Bioquímica de la Provincia de Buenos Aires.

The lytic mechanism of Escherichia coli á-hemolysin associated to outer membrane vesicles.
Herlax, V; Henning, M. F; Bernasconi, A. M; Goñi, F. M; Bakás, L.
2010. Health. Scientific Research Publishing. vol. 2, n°5, p. 484-492. ISSN 1949-4998

Visualization and analysis of lipopolysaccharide distribution in binary phospholipid bilayers.
Henning, M. F; Sanchez, S; Bakas, L.
2009. Biochemical and biophysical research communications. Elsevier, vol.383, p. 22-26

Relevance of fatty acid covalently bound to Escherichia coli alpha-Hemolysin and membrane microdomains in the oligomerization process.
Herlax, V; Maté, S; Rimoldi, O; Bakas, L.
2009. Journal of Biological Chemistry. Amer Soc Biochemistry Molecular Biology, Inc, vol. 284, p. 25199-25210

Fatty acids covalently bound to a-hemolysin of Escherichia coli are involved in the molten globule conformation: Implication of disorder regions in the binding promiscuity.
Herlax, V; Bakas, L.
2007. Biochemistry. vol. 46, p. 5177-5184 ISSN 0006-2960

Paradoxical lipid dependence of pores formed by Escherichia coli α-hemolysin in planar phospholipids bilayer membranas.
Bakás, L; Chanturiya, A; Herlax, V; Zimmerberg, J.
2006. Biophysical J. 91:3748-3755. ISSN: 0006-349591

Role of lipopolisacharide on the structure and function of HlyA from Escherichia coli.
Herlax, V; de Alaniz, M. J.T; Bakás, L.
2005. Chem Phys Lipids. 135(2):107-115. ISSN: 0009-3084

Acyl chains are responsable for irreversibility in the Escherichia coliα-Hemolysin binding to membrane.
Herlax, V; Bakás, L.
2003. Short Communication, Chem.Phys.Lipids 122 185-190. ISSN: 0009-3084

Aplicaciones terapéuticas de toxinas líticas formadoras de poros: potencialidades de a- hemolisina de Escherichia coli.
Herlax, V; Bakás, L.
2001. Medicina, 62:66-72 (artículo especial). ISSN 0025-7680

Hemolisina de Escherichia coli: Prototipo de las toxinas RTX (Repeat in Toxin): Un estudio de las etapas de su mecanismo de acción?
Vázquez, R; Maté, S; Herlax, V; Bakás, L; Pazos Santos, F; Alvarez, C.
2017. p. 191-215. ISBN 978-607-525-046-5

α-Hemolisina de Escherichia coli: Prototipo de las toxinas RTX (Repeat in Toxin). Un estudio de las etapas de su mecanismo de acción.
Vázquez, R; Maté, S; Herlax, V; Bakás, L; Álvarez Valcárcel, C; Pazos Santos, F.
2016. Puebla: Capítulo 8:191-213 en Estrategias y avances en el estudio de toxinas con aplicaciones biomédicas, Eds Dra. Fabiola Pazos Santos y Dr. Carlos Alvarez. Editorial BENEMÉRITA UNIVERSIDAD AUTONOMA DE PUEBLA, México (2015). ISBN: 978-607-525-046-5

Role of sphingomyelin in membrane-domain formation and the influence on protein interaction: focusing on the nanometer scale.
Maté, S; Herlax, V; Vázquez, R; Bakás, L.
2016. Nueva York: NovaScience Publishers, p. 89-112. ISBN 978-1-63484-581-6

E. coli Alpha Hemolysin and Properties.
Bakás, L; Maté, S; Vázquez, R; Herlax, V.
2012. InTech, p. 107-140. ISBN 978-953-51-0076-8
DOI: 10.5772/33383

Interacción lípido-proteína: Mecanismo de acción de alfa hemolisina de E. Coli.
Vanesa Herlax.
2012. Editorial Académica Española, 2012. p. 160

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