Fungicidal Potency and Mechanisms of θ-Defensins against Multidrug-Resistant Candida Species

Antimicrobial Agents and Chemotherapy
Virginia BassoMichael E Selsted

Abstract

Systemic candidiasis is a growing health care concern that is becoming even more challenging due to the growing frequency of infections caused by multidrug-resistant (MDR) Candida species. Thus, there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of θ-defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug-sensitive and drug-resistant clinical isolates of Candida albicans and non-albicans Candida species. Rhesus θ-defensin 1 (RTD-1), the prototype θ-defensin, was rapidly and potently fungicidal against drug-sensitive and MDR C. albicans strains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that by histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 killed C. albicans much more rapidly and at a >200-fold lower concentration than that of Hst 5. Unlike Hst 5, the anticandidal activity of RTD-1 was independent of mitochondrial ATP pr...Continue Reading

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Citations

Nov 7, 2018·Journal of Intensive Care·Andrea CortegianiAnuradha Chowdhary
Oct 22, 2020·Scientific Reports·Makoto SumiyoshiHiroshi Mukae
Nov 5, 2020·MBio·Giuseppe Buda De CesareMichael C Lorenz
Oct 30, 2020·Journal of Fungi·Virginia BassoMichael E Selsted
Jun 29, 2021·Expert Review of Clinical Pharmacology·Daniele R GiacobbeMatteo Bassetti
Jul 3, 2021·Biomolecules·Marija PetkovicHåvard Jenssen

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