Hilpert, K; Rumancev, C; Gani, J; Collis, DWP; Lopez-Perez, PM; Garamus, VM; Mikut, R; Rosenhahn, A
(2023)
Can BioSAXS detect ultrastructural changes of antifungal compounds in Candida albicans?-an exploratory study.
Front Pharmacol, 14.
p. 1141785.
ISSN 1663-9812
https://doi.org/10.3389/fphar.2023.1141785
SGUL Authors: Hilpert, Kai
Abstract
The opportunistic yeast Candida albicans is the most common cause of candidiasis. With only four classes of antifungal drugs on the market, resistance is becoming a problem in the treatment of fungal infections, especially in immunocompromised patients. The development of novel antifungal drugs with different modes of action is urgent. In 2016, we developed a groundbreaking new medium-throughput method to distinguish the effects of antibacterial agents. Using small-angle X-ray scattering for biological samples (BioSAXS), it is now possible to screen hundreds of new antibacterial compounds and select those with the highest probability for a novel mode of action. However, yeast (eukaryotic) cells are highly structured compared to bacteria. The fundamental question to answer was if the ultrastructural changes induced by the action of an antifungal drug can be detected even when most structures in the cell stay unchanged. In this exploratory work, BioSAXS was used to measure the ultrastructural changes of C. albicans that were directly or indirectly induced by antifungal compounds. For this, the well-characterized antifungal drug Flucytosine was used. BioSAXS measurements were performed on the synchrotron P12 BioSAXS beamline, EMBL (DESY, Hamburg) on treated and untreated yeast C. albicans. BioSAXS curves were analysed using principal component analysis (PCA). The PCA showed that Flucytosine-treated and untreated yeast were separated. Based on that success further measurements were performed on five antifungal peptides {1. Cecropin A-melittin hybrid [CA (1-7) M (2-9)], KWKLFKKIGAVLKVL; 2. Lasioglossin LL-III, VNWKKILGKIIKVVK; 3. Mastoparan M, INLKAIAALAKKLL; 4. Bmkn2, FIGAIARLLSKIFGKR; and 5. optP7, KRRVRWIIW}. The ultrastructural changes of C. albicans indicate that the peptides may have different modes of action compared to Flucytosine as well as to each other, except for the Cecropin A-melittin hybrid [CA (1-7) M (2-9)] and optP7, showing very similar effects on C. albicans. This very first study demonstrates that BioSAXS shows promise to be used for antifungal drug development. However, this first study has limitations and further experiments are necessary to establish this application.
Item Type: |
Article
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Additional Information: |
Copyright © 2023 Hilpert, Rumancev, Gani, Collis, Lopez-Perez, Garamus, Mikut and Rosenhahn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: |
BioSAXS, Candida albicans, SAXS (small-angle X-ray scattering), antifungal peptides, antimicrobial peptides, mode of action (MOA), Candida albicans, antifungal peptides, antimicrobial peptides, BioSAXS, SAXS (small-angle X-ray scattering), mode of action (MOA), 1115 Pharmacology and Pharmaceutical Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Front Pharmacol |
ISSN: |
1663-9812 |
Language: |
eng |
Dates: |
Date | Event |
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18 July 2023 | Published | 6 July 2023 | Accepted |
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Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
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PubMed ID: |
37533629 |
Web of Science ID: |
WOS:001040953600001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/115729 |
Publisher's version: |
https://doi.org/10.3389/fphar.2023.1141785 |
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