Cationic Amphiphiles Induce Macromolecule Denaturation and Organelle Decomposition in Pathogenic Yeast

Qais Z. Jaber, Raphael I. Benhamou, Ido M. Herzog, Bar Ben Baruch, Micha Fridman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Cationic amphiphiles are a large and diverse class of antimicrobial agents. Although their mode of action is not fully resolved, it is generally accepted that these antimicrobials perturb the structural integrity of the plasma membrane leading to the microbial cell disruption. Here we report on the development of inherently fluorescent antifungal cationic amphiphiles and on the study of their effects on cells of Candida, one of the most common fungal pathogens in humans. Fluorescent images of Candida yeast cells that express a fluorescent reporter protein revealed that the cationic amphiphiles rapidly accumulated in the cytosol and led to structural changes in proteins and DNA. Using fluorescent organelle-specific dyes, we showed that these antifungal agents also caused organelle disassembly in Candida cells. The results of this study indicate that, in designing antifungal cationic amphiphiles for clinical use, the intracellular activities of these molecules must be addressed to avoid undesired side effects to mammalian cells.

Original languageAmerican English
Pages (from-to)16391-16395
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number50
DOIs
StatePublished - 10 Dec 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • amphiphilic aminoglycosides
  • antifungal amphiphiles
  • antimicrobial amphiphiles
  • fluorogenic probes
  • membrane disrupting agents

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