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Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Graz, Austria.
Number of Authors: 32018 (English)In: Oxford Journal of Law and Religion, ISSN 1942-0900, E-ISSN 2326-8344, Vol. 2018, article id 5473817Article, review/survey (Refereed) Published
Abstract [en]

The rise of microbial pathogens refractory to conventional antibiotics represents one of the most urgent and global public health concerns for the 21st century. Emergence of Candida auris isolates and the persistence of invasive mold infections that resist existing treatment and cause severe illness has underscored the threat of drug-resistant fungal infections. To meet these growing challenges, mechanistically novel agents and strategies are needed that surpass the conventional fungistatic or fungicidal drug actions. Host defense peptides have long been misunderstood as indiscriminant membrane detergents. However, evidence gathered over the past decade clearly points to their sophisticated and selective mechanisms of action, including exploiting regulated cell death pathways of their target pathogens. Such peptides perturb transmembrane potential and mitochondrial energetics, inducing phosphatidylserine accessibility and metacaspase activation in fungi. These mechanisms are often multimodal, affording target pathogens fewer resistance options as compared to traditional small molecule drugs. Here, recent advances in the field are examined regarding regulated cell death subroutines as potential therapeutic targets for innovative anti-infective peptides against pathogenic fungi. Furthering knowledge of protective host defense peptide interactions with target pathogens is key to advancing and applying novel prophylactic and therapeutic countermeasures to fungal resistance and pathogenesis.

Place, publisher, year, edition, pages
2018. Vol. 2018, article id 5473817
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-156709DOI: 10.1155/2018/5473817ISI: 000431660300001OAI: oai:DiVA.org:su-156709DiVA, id: diva2:1210460
Available from: 2018-05-28 Created: 2018-05-28 Last updated: 2018-05-28Bibliographically approved

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