Design strategies for positively charged endolysins : Insights into Artilysin development
Carratalá, José Vicente (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Arís i Giralt, Anna (Institut de Recerca i Tecnologia Agroalimentàries)
Garcia-Fruitos, Elena (Institut de Recerca i Tecnologia Agroalimentàries)
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Data:	2023
Resum:	Endolysins are bacteriophage-encoded enzymes that can specifically degrade the peptidoglycan layer of bacterial cell wall, making them an attractive tool for the development of novel antibacterial agents. The use of genetic engineering techniques for the production and modification of endolysins offers the opportunity to customize their properties and activity against specific bacterial targets, paving the way for the development of personalized therapies for bacterial infections. Gram-negative bacteria possess an outer membrane that can hinder the action of recombinantly produced endolysins. However, certain endolysins are capable of crossing the outer membrane by virtue of segments that share properties resembling those of cationic peptides. These regions increase the affinity of the endolysin towards the bacterial surface and assist in the permeabilization of the membrane. In order to improve the bactericidal effectiveness of endolysins, approaches have been implemented to increase their net charge, including the development of Artilysins containing positively charged amino acids at one end. At present, there are no specific guidelines outlining the steps for implementing these modifications. There is an ongoing debate surrounding the optimal location of positive charge, the need for a linker region, and the specific amino acid composition of peptides for modifying endolysins. The aim of this study is to provide clarity on these topics by analyzing and comparing the most effective modifications found in previous literature.
Ajuts:	Agencia Estatal de Investigación PID2019-107298RB-C21 Agencia Estatal de Investigación PID2019-107298RB-C22 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01552 Fundació la Marató de TV3 201812-30-31-32-33
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	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, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Endolysins ; Antibacterial agents ; Gram-negative bacteria ; Outer membrane ; Cationic peptides ; Artilysins ; Protein engineering
Publicat a:	Biotechnology advances, Vol. 69 (December 2023) , art. 108250, ISSN 0734-9750

DOI: 10.1016/j.biotechadv.2023.108250

14 p, 6.9 MB

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