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Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent

The identification and development of natural products into novel antimicrobial agents is crucial to combat the rise of multidrug-resistant microorganisms. Clinical fungal isolates have been identified, which have shown resistance to all current clinical antifungals, highlighting a significant need...

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Autores principales: Hansanant, Nopakorn, Smith, Leif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494966/
https://www.ncbi.nlm.nih.gov/pubmed/36139923
http://dx.doi.org/10.3390/antibiotics11091143
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author Hansanant, Nopakorn
Smith, Leif
author_facet Hansanant, Nopakorn
Smith, Leif
author_sort Hansanant, Nopakorn
collection PubMed
description The identification and development of natural products into novel antimicrobial agents is crucial to combat the rise of multidrug-resistant microorganisms. Clinical fungal isolates have been identified, which have shown resistance to all current clinical antifungals, highlighting a significant need to develop a novel antifungal agent. One of the natural products produced by the bacterium Burkholderia contaminans MS14 is the glycolipopeptide occidiofungin. Occidiofungin has demonstrated in vitro activity against a multitude of fungal species, including multidrug-resistant Candida auris strains, and in vivo effectiveness in treating vulvovaginal candidiasis. Characterization of occidiofungin revealed the mechanism of action as binding to actin to disrupt higher-order actin-mediated functions leading to the induction of apoptosis in fungal cells. Occidiofungin is the first small molecule capable of disrupting higher-order actin functions and is a first-in-class compound that is able to circumvent current antifungal resistant mechanisms by fungal species. Anticancer properties and antiparasitic activities, against Cryptosporidium parvum, have also been demonstrated in vitro. The novel mechanism of action and wide spectrum of activity highlights the potential of occidiofungin to be developed for clinical use.
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spelling pubmed-94949662022-09-23 Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent Hansanant, Nopakorn Smith, Leif Antibiotics (Basel) Review The identification and development of natural products into novel antimicrobial agents is crucial to combat the rise of multidrug-resistant microorganisms. Clinical fungal isolates have been identified, which have shown resistance to all current clinical antifungals, highlighting a significant need to develop a novel antifungal agent. One of the natural products produced by the bacterium Burkholderia contaminans MS14 is the glycolipopeptide occidiofungin. Occidiofungin has demonstrated in vitro activity against a multitude of fungal species, including multidrug-resistant Candida auris strains, and in vivo effectiveness in treating vulvovaginal candidiasis. Characterization of occidiofungin revealed the mechanism of action as binding to actin to disrupt higher-order actin-mediated functions leading to the induction of apoptosis in fungal cells. Occidiofungin is the first small molecule capable of disrupting higher-order actin functions and is a first-in-class compound that is able to circumvent current antifungal resistant mechanisms by fungal species. Anticancer properties and antiparasitic activities, against Cryptosporidium parvum, have also been demonstrated in vitro. The novel mechanism of action and wide spectrum of activity highlights the potential of occidiofungin to be developed for clinical use. MDPI 2022-08-23 /pmc/articles/PMC9494966/ /pubmed/36139923 http://dx.doi.org/10.3390/antibiotics11091143 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hansanant, Nopakorn
Smith, Leif
Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent
title Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent
title_full Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent
title_fullStr Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent
title_full_unstemmed Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent
title_short Occidiofungin: Actin Binding as a Novel Mechanism of Action in an Antifungal Agent
title_sort occidiofungin: actin binding as a novel mechanism of action in an antifungal agent
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494966/
https://www.ncbi.nlm.nih.gov/pubmed/36139923
http://dx.doi.org/10.3390/antibiotics11091143
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