Abstract
Trichophyton rubrum (T. rubrum) is the commonest causative agent of dermatophytosis worldwide. Development of anti-fungal
drugs will contribute to treating the disease. Here we suggest a hemiprotonic compound
phenanthroline- phenanthroline+ (ph-ph+), is active in inhibiting the growth and reproduction of T. rubrum, and the values of MIC and MFC were 2 μg/mL and 8 μg/mL, respectively. In vitro onychomycosis model, ph-ph+ killed T. rubrum by inducing apoptosis, evaluated by TEM and Annexin V-FITC/PI staining. Transcriptomic
analysis and biochemical assay showed that ph-ph+ elevated iron ion content in T. rubrum cells and reduced GSH antioxidant system level, leading to increase in the contents
of ROS and MDA. Therefore, the anti-fungal mechanism of ph-ph+ would be associated with iron ion-induced cell apoptosis, which is different from
other known anti-fungal drugs. Further, ph-ph+ was prepared into gel for application in guinea pigs with dermatophytosis caused
by T. rubrum. The results showed that the ph-ph+ gel eliminated the fungus in the animals, without skin irritation and other adverse
reactions. The study would not only provide potential compound to treat dermatophytosis,
but also suggests that iron ion-induced cell apoptosis might be a new approach to
kill fungi.
Graphical abstract
Graphical Abstract
Keywords
Abbreviations:
ATP (adenosine-triphosphate), ANOVA (one-way analysis of variance), CFUs (colony forming units), CLSI (Clinical and Laboratory Standards Institute), DEGs (differentially expressed genes), FITC (fluorescein), GO (gene ontology), GSH (glutathione), GSH-PX (glutathione peroxidase), HE staining (hematoxylin-eosin staining), HPLC (high performance liquid chromatography), KEGG (Kyoto encyclopedia of genes and genomes), MBC (minimal bactericidal concentration), MDA (malondialdehyde), MFC (minimal fungicidal concentration), MIC (minimum inhibitory concentration), MMP (mitochondrial membrane potential), PAS staining (periodic acid-Schiff staining), ph-ph+ (phenanthroline-phenanthroline+), PI (propidium iodide), ROS (reactive oxygen species), SD (standard deviation), SDM (Sabouraud dextrose medium), TEM (transmission electron microscope), T. rubrum (Trichophyton rubrum)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
February 16,
2023
Received in revised form:
February 15,
2023
Received:
November 11,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Data availability statement
All data generated or used during the study are available from the corresponding author upon request. Datasets related to this article can be found at https://data.mendeley.com/datasets/7z8d7yt663/1, an open-source online data repository hosted at Mendeley Data.
Conflicts of Interest
The authors state no conflict of interest.
CRediT statement
Conceptualization: AF; Methodology: YZ, JL, ZZ; Investigation: ZZ, XY, DY; Writing – Original Draft Preparation: XL, ZF; Writing - Review and Editing: AF, YZ, JL, ZZ.
Identification
Copyright
© 2023 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
