English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/135032
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

AutorCampos-Salinas, Jenny; Cavazzuti, A.; O'Valle, Francisco; Forte-Lago, Irene; Caro, Marta; Beverley, S. M.; Delgado, M.; González-Rey, Elena
Palabras claveAntimicrobial Peptides
Lipopolysaccharide (LPS)
Vasoactive Intestinal Peptide
Cutaneous Leishmaniasis
Fecha de publicación4-abr-2014
EditorAmerican Society for Biochemistry and Molecular Biology
CitaciónJournal of Biological Chemistry
ResumenVasoactive intestinal peptide (VIP) is an anti-inflammatory neuropeptide recently identified as a potential antimicrobial peptide. To overcome the metabolic limitations of VIP, we modified the native peptide sequence and generated two stable synthetic analogues (VIP51 and VIP51(6–30)) with better antimicrobial profiles. Herein we investigate the effects of both VIP analogues on cell viability, membrane integrity, and ultrastructure of various bacterial strains and Leishmania species. We found that the two VIP derivatives kill various non-pathogenic and pathogenic Gram-positive and Gram-negative bacteria as well as the parasite Leishmania major through a mechanism that depends on the interaction with certain components of the microbial surface, the formation of pores, and the disruption of the surface membrane. The cytotoxicity of the VIP derivatives is specific for pathogens, because they do not affect the viability of mammalian cells. Docking simulations indicate that the chemical changes made in the analogues are critical to increase their antimicrobial activities. Consequently, we found that the native VIP is less potent as an antibacterial and fails as a leishmanicidal. Noteworthy from a therapeutic point of view is that treatment with both derivatives increases the survival and reduces bacterial load and inflammation in mice with polymicrobial sepsis. Moreover, treatment with VIP51(6–30) is very effective at reducing lesion size and parasite burden in a model of cutaneous leishmaniasis. These results indicate that the VIP analogues emerge as attractive alternatives for treating drug-resistant infectious diseases and provide key insights into a rational design of novel agents against these pathogens.
Versión del editorhttp://www.jbc.org/content/early/2014/04/04/jbc.M114.560573
Aparece en las colecciones: (IPBLN) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
J. Biol. Chem.-2014-Campos-Salinas-14583-99 (2).pdf4,01 MBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.