Essential Role of Enzymatic Activity in the Leishmanicidal Mechanism of the Eosinophil Cationic Protein (RNase 3)
Abengozar, María Ángeles (Centro de Investigaciones Biológicas (Madrid))
Fernández-Reyes, María (Centro de Investigaciones Biológicas (Madrid))
Salazar, V. A. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Torrent, Marc (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
de la Torre, Beatriz G. (Universitat Pompeu Fabra)
Andreu Martínez, David (Universitat Pompeu Fabra)
Boix, Ester (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Rivas, Luis (Centro de Investigaciones Biológicas (Madrid))

Date:	2022
Abstract:	The recruitment of eosinophils into Leishmania lesions is frequently associated with a favorable evolution. A feasible effector for this process is eosinophil cationic protein (ECP, RNase 3), one of the main human eosinophil granule proteins, endowed with a broad spectrum of antimicrobial activity, including parasites. ECP was active on Leishmania promastigotes and axenic amastigotes (LC's = 3 and 16 μM, respectively) but, in contrast to the irreversible membrane damage caused on bacteria and reproduced by its N -terminal peptides, it only induced a mild and transient plasma membrane destabilization on Leishmania donovani promastigotes. To assess the contribution of RNase activity to the overall leishmanicidal activity of ECP, parasites were challenged in parallel with a single-mutant version, ECP-H15A, devoid of RNase activity, that fully preserves the conformation and liposome permeabilization ability. ECP-H15A showed a similar uptake to ECP on promastigotes, but with higher LC's (.
Grants:	Agencia Estatal de Investigación PID2019-108166GB-I00 Ministerio de Ciencia e Innovación SAF2011-24899 Ministerio de Economía y Competitividad RD16/0027/0010 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-492
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Membrane disruption ; Cell-penetrating enzyme ; Antimicrobial peptide ; RNase ; Protozoa
Published in:	ACS infectious diseases, Vol. 8, Issue 7 (July 2022) , p. 1207-1217, ISSN 2373-8227

DOI: 10.1021/acsinfecdis.1c00537
PMID: 35731709

11 p, 5.2 MB

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