Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides

ABSTRACT AFP is an antimicrobial peptide (AMP) produced by the filamentous fungus Aspergillus giganteus and is a very potent inhibitor of fungal growth that does not affect the viability of bacteria, plant, or mammalian cells. It targets chitin synthesis and causes plasma membrane permeabilization i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Norman Paege, Dirk Warnecke, Simone Zäuner, Silke Hagen, Ana Rodrigues, Birgit Baumann, Melanie Thiess, Sascha Jung, Vera Meyer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	antimicrobial peptide antifungal protein AFP gamma core damage-response framework sphingolipid glycosylceramide Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5daaa7a311104ac281f9e46d9e7e3a5f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5daaa7a311104ac281f9e46d9e7e3a5f
record_format	dspace
spelling	oai:doaj.org-article:5daaa7a311104ac281f9e46d9e7e3a5f2021-11-15T15:22:24ZSpecies-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides10.1128/mSphere.00741-192379-5042https://doaj.org/article/5daaa7a311104ac281f9e46d9e7e3a5f2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00741-19https://doaj.org/toc/2379-5042ABSTRACT AFP is an antimicrobial peptide (AMP) produced by the filamentous fungus Aspergillus giganteus and is a very potent inhibitor of fungal growth that does not affect the viability of bacteria, plant, or mammalian cells. It targets chitin synthesis and causes plasma membrane permeabilization in many human- and plant-pathogenic fungi, but its exact mode of action is not known. After adoption of the “damage-response framework of microbial pathogenesis” regarding the analysis of interactions between AMPs and microorganisms, we have recently proposed that the cytotoxic capacity of a given AMP depends not only on the presence/absence of its target(s) in the host and the AMP concentration applied but also on other variables, such as microbial survival strategies. We show here using the examples of three filamentous fungi (Aspergillus niger, Aspergillus fumigatus, and Fusarium graminearum) and two yeasts (Saccharomyces cerevisiae and Pichia pastoris) that the important parameters defining the AFP susceptibilities of these fungi are (i) the presence/absence of glycosylceramides, (ii) the presence/absence of Δ3(E) desaturation of the fatty acid chain therein, and (iii) the (dis)ability of these fungi to respond to AFP inhibitory effects with the fortification of their cell walls via increased chitin and β-(1,3)-glucan synthesis. These observations support the idea of the adoption of the damage-response framework to holistically understand the outcome of AFP inhibitory effects. IMPORTANCE Our data suggest a fundamental role of glycosylceramides in the susceptibility of fungi to AFP. We discovered that only a minor structural difference in these molecules—namely, the saturation level of their fatty acid chain, controlled by a 2-hydroxy fatty N-acyl-Δ3(E)-desaturase—represents a key to understanding the inhibitory activity of AFP. As glycosylceramides are important components of fungal plasma membranes, we propose a model which links AFP-mediated inhibition of chitin synthesis in fungi with its potential to disturb plasma membrane integrity.Norman PaegeDirk WarneckeSimone ZäunerSilke HagenAna RodriguesBirgit BaumannMelanie ThiessSascha JungVera MeyerAmerican Society for Microbiologyarticleantimicrobial peptideantifungal protein AFPgamma coredamage-response frameworksphingolipidglycosylceramideMicrobiologyQR1-502ENmSphere, Vol 4, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial peptide antifungal protein AFP gamma core damage-response framework sphingolipid glycosylceramide Microbiology QR1-502
spellingShingle	antimicrobial peptide antifungal protein AFP gamma core damage-response framework sphingolipid glycosylceramide Microbiology QR1-502 Norman Paege Dirk Warnecke Simone Zäuner Silke Hagen Ana Rodrigues Birgit Baumann Melanie Thiess Sascha Jung Vera Meyer Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides
description	ABSTRACT AFP is an antimicrobial peptide (AMP) produced by the filamentous fungus Aspergillus giganteus and is a very potent inhibitor of fungal growth that does not affect the viability of bacteria, plant, or mammalian cells. It targets chitin synthesis and causes plasma membrane permeabilization in many human- and plant-pathogenic fungi, but its exact mode of action is not known. After adoption of the “damage-response framework of microbial pathogenesis” regarding the analysis of interactions between AMPs and microorganisms, we have recently proposed that the cytotoxic capacity of a given AMP depends not only on the presence/absence of its target(s) in the host and the AMP concentration applied but also on other variables, such as microbial survival strategies. We show here using the examples of three filamentous fungi (Aspergillus niger, Aspergillus fumigatus, and Fusarium graminearum) and two yeasts (Saccharomyces cerevisiae and Pichia pastoris) that the important parameters defining the AFP susceptibilities of these fungi are (i) the presence/absence of glycosylceramides, (ii) the presence/absence of Δ3(E) desaturation of the fatty acid chain therein, and (iii) the (dis)ability of these fungi to respond to AFP inhibitory effects with the fortification of their cell walls via increased chitin and β-(1,3)-glucan synthesis. These observations support the idea of the adoption of the damage-response framework to holistically understand the outcome of AFP inhibitory effects. IMPORTANCE Our data suggest a fundamental role of glycosylceramides in the susceptibility of fungi to AFP. We discovered that only a minor structural difference in these molecules—namely, the saturation level of their fatty acid chain, controlled by a 2-hydroxy fatty N-acyl-Δ3(E)-desaturase—represents a key to understanding the inhibitory activity of AFP. As glycosylceramides are important components of fungal plasma membranes, we propose a model which links AFP-mediated inhibition of chitin synthesis in fungi with its potential to disturb plasma membrane integrity.
format	article
author	Norman Paege Dirk Warnecke Simone Zäuner Silke Hagen Ana Rodrigues Birgit Baumann Melanie Thiess Sascha Jung Vera Meyer
author_facet	Norman Paege Dirk Warnecke Simone Zäuner Silke Hagen Ana Rodrigues Birgit Baumann Melanie Thiess Sascha Jung Vera Meyer
author_sort	Norman Paege
title	Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides
title_short	Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides
title_full	Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides
title_fullStr	Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides
title_full_unstemmed	Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides
title_sort	species-specific differences in the susceptibility of fungi to the antifungal protein afp depend on c-3 saturation of glycosylceramides
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/5daaa7a311104ac281f9e46d9e7e3a5f
work_keys_str_mv	AT normanpaege speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT dirkwarnecke speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT simonezauner speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT silkehagen speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT anarodrigues speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT birgitbaumann speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT melaniethiess speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT saschajung speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides AT verameyer speciesspecificdifferencesinthesusceptibilityoffungitotheantifungalproteinafpdependonc3saturationofglycosylceramides
_version_	1718428009563684864

Species-Specific Differences in the Susceptibility of Fungi to the Antifungal Protein AFP Depend on C-3 Saturation of Glycosylceramides

Ejemplares similares