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Alexidine Dihydrochloride Has Broad-Spectrum Activities against Diverse Fungal Pathogens

Authors: Mamouei, Zeinab; Alqarihi, Abdullah; Singh, Shakti; Xu, Shuying; Mansour, Michael K; Ibrahim, Ashraf S; Uppuluri, Priya;

Alexidine Dihydrochloride Has Broad-Spectrum Activities against Diverse Fungal Pathogens

Abstract

The prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multidrug-resistant strains such as C. auris . High mortality related to fungal infections points to major limitations of current antifungal therapy and an unmet need for new antifungal drugs. We screened a library of repurposed FDA-approved inhibitors to identify compounds with activities against a diverse range of fungi in varied phases of growth. The assays identified alexidine dihydrochloride (AXD) to have pronounced antifungal activity, including against preformed biofilms, at concentrations lower than mammalian cell toxicity. AXD potentiated the activity of fluconazole and amphotericin B against Candida biofilms in vitro and prevented biofilm growth in vivo . Thus, AXD has the potential to be developed as a pan-antifungal, antibiofilm drug.

Country
United States
Keywords

Antifungal Agents, Immunology, Biguanides, Drug Evaluation, Preclinical, Microbiology, Vaccine Related, Small Molecule Libraries, Mice, Models, Biodefense, Candida albicans, 2.2 Factors relating to the physical environment, Animals, Central Venous Catheters, Aetiology, Fluconazole, Candida, Microbial Viability, Animal, Prevention, Aspergillus fumigatus, Drug Synergism, Preclinical, QR1-502, panfungal, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, 5.1 Pharmaceuticals, Biofilms, Models, Animal, Drug Evaluation, antifungal agents, Antimicrobial Resistance, HTS, Development of treatments and therapeutic interventions, biofilms, Infection, FDA, Research Article

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    50
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
50
Top 10%
Top 10%
Top 10%
Green
gold