Fungicidal Activity of Recombinant Javanicin against Cryptococcus neoformans Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes

The occurrence of Cryptococcus neoformans, the human fungal pathogen that primarily infects immunocompromised individuals, has been progressing at an alarming rate. The increased incidence of infection of C. neoformans with antifungal drugs resistance has become...

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Autores principales:	Santhasiri Orrapin, Sittiruk Roytrakul, Narumon Phaonakrop, Siriwan Thaisakun, Khajornsak Tragoolpua, Amornrat Intorasoot, Suzanne McGill, Richard Burchmore, Sorasak Intorasoot
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	plant defensin javanicin <i>Cryptococcus neoformans</i> antifungal action proteomics Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/a069528d97a44eabb9d75171c2c46914
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spelling	oai:doaj.org-article:a069528d97a44eabb9d75171c2c469142021-11-25T18:29:11ZFungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes10.3390/molecules262270111420-3049https://doaj.org/article/a069528d97a44eabb9d75171c2c469142021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7011https://doaj.org/toc/1420-3049The occurrence of <i>Cryptococcus neoformans</i>, the human fungal pathogen that primarily infects immunocompromised individuals, has been progressing at an alarming rate. The increased incidence of infection of <i>C. neoformans</i> with antifungal drugs resistance has become a global concern. Potential antifungal agents with extremely low toxicity are urgently needed. Herein, the biological activities of recombinant javanicin (r-javanicin) against <i>C. neoformans</i> were evaluated. A time-killing assay was performed and both concentration- and time-dependent antifungal activity of r-javanicin were indicated. The inhibitory effect of the peptide was initially observed at 4 h post-treatment and ultimately eradicated within 36 to 48 h. Fungal outer surface alteration was characterized by the scanning electron microscope (SEM) whereas a negligible change with slight shrinkage of external morphology was observed in r-javanicin treated cells. Confocal laser scanning microscopic analysis implied that the target(s) of r-javanicin is conceivably resided in the cell thereby allowing the peptide to penetrate across the membrane and accumulate throughout the fungal body. Finally, cryptococcal cells coped with r-javanicin were preliminarily investigated using label-free mass spectrometry-based proteomics. Combined with microscopic and proteomics analysis, it was clearly elucidated the peptide localized in the intracellular compartment where carbohydrate metabolism and energy production associated with glycolysis pathway and mitochondrial respiration, respectively, were principally interfered. Overall, r-javanicin would be an alternative candidate for further development of antifungal agents.Santhasiri OrrapinSittiruk RoytrakulNarumon PhaonakropSiriwan ThaisakunKhajornsak TragoolpuaAmornrat IntorasootSuzanne McGillRichard BurchmoreSorasak IntorasootMDPI AGarticleplant defensinjavanicin<i>Cryptococcus neoformans</i>antifungal actionproteomicsOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 7011, p 7011 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	plant defensin javanicin <i>Cryptococcus neoformans</i> antifungal action proteomics Organic chemistry QD241-441
spellingShingle	plant defensin javanicin <i>Cryptococcus neoformans</i> antifungal action proteomics Organic chemistry QD241-441 Santhasiri Orrapin Sittiruk Roytrakul Narumon Phaonakrop Siriwan Thaisakun Khajornsak Tragoolpua Amornrat Intorasoot Suzanne McGill Richard Burchmore Sorasak Intorasoot Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
description	The occurrence of <i>Cryptococcus neoformans</i>, the human fungal pathogen that primarily infects immunocompromised individuals, has been progressing at an alarming rate. The increased incidence of infection of <i>C. neoformans</i> with antifungal drugs resistance has become a global concern. Potential antifungal agents with extremely low toxicity are urgently needed. Herein, the biological activities of recombinant javanicin (r-javanicin) against <i>C. neoformans</i> were evaluated. A time-killing assay was performed and both concentration- and time-dependent antifungal activity of r-javanicin were indicated. The inhibitory effect of the peptide was initially observed at 4 h post-treatment and ultimately eradicated within 36 to 48 h. Fungal outer surface alteration was characterized by the scanning electron microscope (SEM) whereas a negligible change with slight shrinkage of external morphology was observed in r-javanicin treated cells. Confocal laser scanning microscopic analysis implied that the target(s) of r-javanicin is conceivably resided in the cell thereby allowing the peptide to penetrate across the membrane and accumulate throughout the fungal body. Finally, cryptococcal cells coped with r-javanicin were preliminarily investigated using label-free mass spectrometry-based proteomics. Combined with microscopic and proteomics analysis, it was clearly elucidated the peptide localized in the intracellular compartment where carbohydrate metabolism and energy production associated with glycolysis pathway and mitochondrial respiration, respectively, were principally interfered. Overall, r-javanicin would be an alternative candidate for further development of antifungal agents.
format	article
author	Santhasiri Orrapin Sittiruk Roytrakul Narumon Phaonakrop Siriwan Thaisakun Khajornsak Tragoolpua Amornrat Intorasoot Suzanne McGill Richard Burchmore Sorasak Intorasoot
author_facet	Santhasiri Orrapin Sittiruk Roytrakul Narumon Phaonakrop Siriwan Thaisakun Khajornsak Tragoolpua Amornrat Intorasoot Suzanne McGill Richard Burchmore Sorasak Intorasoot
author_sort	Santhasiri Orrapin
title	Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
title_short	Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
title_full	Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
title_fullStr	Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
title_full_unstemmed	Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes
title_sort	fungicidal activity of recombinant javanicin against <i>cryptococcus neoformans</i> is associated with intracellular target(s) involved in carbohydrate and energy metabolic processes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a069528d97a44eabb9d75171c2c46914
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Fungicidal Activity of Recombinant Javanicin against <i>Cryptococcus neoformans</i> Is Associated with Intracellular Target(s) Involved in Carbohydrate and Energy Metabolic Processes

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