Fungal Infections and Antifungals

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 692

Special Issue Editor


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Guest Editor
Center for Medical Sciences, Federal University of Pernambuco (UFPE), Recife, Brazil
Interests: fungal pathogenesis; antimicrobial resistance; antibiotics; antibacterial agents; molecular pharmacology

Special Issue Information

Dear Colleagues,

Fungal infections affect more than one billion people annually, with mortality rates similar to those of tuberculosis and malaria. Among these infections, those caused by Candida species have increased significantly, with growing concern about spreading potentially fatal fungal diseases. In this regard, the current diagnosis is nonspecific and treatment is sometimes ineffective. In parallel, this scenario may be strongly related to the virulence potential of these microorganisms and also to the patient's innate immune deficiencies. Furthermore, the occurrence of resistant strains has become a major concern, since many of these species have demonstrated reduced susceptibility to commercially available antifungals, which is particularly a problem in clinical settings. Thus, the search for alternative therapies associated with more assertive and rapid diagnostic techniques is crucial to addressing this problem, with the need for studies aimed at understanding the mechanisms of action, epidemiology, resistance to antifungals, and pathogenesis.

Prof. Dr. Rejane Pereira Neves
Guest Editor

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Keywords

  • fungal infections
  • pathogenesis
  • antifungal resistance
  • virulence
  • diagnosis
  • epidemiology

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Published Papers (1 paper)

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10 pages, 1659 KB  
Brief Report
Pathogen Enzyme-Mediated Alkoxyamine Homolysis as a Killing Mechanism of Aspergillus fumigatus
by Marion Filliâtre, Pierre Voisin, Seda Seren, Ines Kelkoul, Olivier Glehen, Philippe Mellet, Sophie Thétiot-Laurent, Jean Menotti, Sylvain R. A. Marque, Gérard Audran and Abderrazzak Bentaher
J. Fungi 2025, 11(7), 503; https://doi.org/10.3390/jof11070503 - 4 Jul 2025
Viewed by 562
Abstract
The emergence of antifungal-resistant Aspergillus fumigatus (A. fumigatus) became a serious public health concern, underscoring the need for new effective antifungal agents. Here, we present a strategy based on the in situ generation of radical species that are toxic to the pathogen. The [...] Read more.
The emergence of antifungal-resistant Aspergillus fumigatus (A. fumigatus) became a serious public health concern, underscoring the need for new effective antifungal agents. Here, we present a strategy based on the in situ generation of radical species that are toxic to the pathogen. The synthesis of an alkoxyamine linked to a peptide substrate recognized by A. fumigatus-secreted dipeptidyl peptidase is described. Kinetic experiments show a stable prodrug prior to enzymatic activation. Ensuing peptide cleavage and spontaneous homolysis resulted in the generation of a stable nitroxide and a reactive alkyl radical moiety. Next, the exposure of A. fumigatus spores to the prodrug lead to pathogen growth inhibition in a compound concentration-dependent fashion (e.g., 42% inhibition at 10 µg/L). Importantly, the designed alkoxyamine inhibited not only the growth of a clinical voriconazole-susceptible A. fumigatus strain, but also the growth of a strain resistant to this azole. To determine the antifungal importance of the reactive alkyl radical, its substitution with a non-radical structure did not prevent A. fumigatus growth. Furthermore, the introduction of succinic group in the peptide substrate resulted in the loss of alkoxyamine antifungal properties. Our work reports a novel chemical strategy for antifungal therapy against A. fumigatus based on the pathogen enzyme-mediated generation of toxic radicals. Significantly, these findings are timely since they could overcome the emerged resistance to conventional drugs that are known to target defined pathogen biologic mechanisms such as ergosterol synthesis. Full article
(This article belongs to the Special Issue Fungal Infections and Antifungals)
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