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Host–Fungal Interplay: Virulence, Immunity, Antifungal Resistance, and Therapeutic Strategies
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Host–Fungal Interplay: Virulence, Immunity, Antifungal Resistance, and Therapeutic Strategies

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: 10 August 2026 | Viewed by 4164

Special Issue Editors

Dr. Claudia Elena Sotomayor

E-Mail Website
Guest Editor
1. CIBICI-CONICET, Laboratory of Innate Immunity to Fungal Pathogens, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
2. Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
Interests: fungal infections; fungal pathogenesis; host immune response
Dr. Juan Pablo Caeiro

E-Mail Website
Guest Editor
HIV/Infectious Diseases Services at AltaMed, Los Angeles, CA 90022, USA
Interests: infectious diseases; fungal infections; novel therapeutics
Dr. Fernando Oscar Riera

E-Mail
Guest Editor
Primera Cátedra de Clínica Infectológica. Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Interests: fungal infections; antifungal resistance; therapeutic approaches

Special Issue Information

Dear Colleagues,

The incidence of fungal infections is rising, posing significant challenges for both clinicians and researchers. The complexity of these infections demands a deeper understanding of fungal pathogenesis, host immune responses, and treatment strategies. Over the years, advancements in key aspects of fungal research have led to tangible progress in disease management.

In this Special Issue, we invite you to explore and discuss novel and relevant aspects of these versatile pathogens, including their virulence mechanisms, host defense strategies, the alarming rise in antifungal resistance, and innovative therapeutic approaches. We cordially invite you to contribute to this collection by sharing your latest findings and insights. Your work will help drive forward our understanding of fungal infections and pave the way for improved clinical strategies.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Fungal pathogenesis;
  • Host immune response;
  • Innate immunity;
  • Virulence factors;
  • Biofilms;
  • Antifungal resistance;
  • Therapeutic approaches;
  • Immunomodulation;
  • Novel therapeutics;
  • Emerging fungal pathogens.

Dr. Claudia Elena Sotomayor
Dr. Juan Pablo Caeiro
Dr. Fernando Oscar Riera
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fungal pathogenesis
  • host immune response
  • antifungal resistance
  • therapeutic approaches
  • emerging fungal pathogens

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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20 pages, 2490 KB  
Article
Biphasic Regulation of Epithelial Antimicrobial Peptides During Candida albicans Vaginal Infection: Distinct Contributions of NLRP3/IL-1β and IL-17RA Pathways to β-Defensin-1 and -3 Expression
by Sofía Carla Angiolini, Emilse Rodriguez, Clarisa Manzone-Rodriguez, Paula Alejandra Icely, María Soledad Miró, Fernando Oscar Riera, Pablo Iribarren, Juan Pablo Caeiro and Claudia Elena Sotomayor
J. Fungi 2026, 12(3), 204; https://doi.org/10.3390/jof12030204 - 11 Mar 2026
Viewed by 689
Abstract
Candida albicans is the primary agent of acute vulvovaginal candidiasis (VVC) and its recurrent form (RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins (BD) constitute key components of the mucosal barrier. We previously reported [...] Read more.
Candida albicans is the primary agent of acute vulvovaginal candidiasis (VVC) and its recurrent form (RVVC). Local innate immunity contributes to both defense and pathogenesis during vaginal Candida infection, where epithelial β-defensins (BD) constitute key components of the mucosal barrier. We previously reported that epithelial BD-1 expression is dynamically modulated during murine and human vaginitis, revealing strain-dependent and stimulus-specific regulation but leaving the host pathways involved unresolved. This study functionally defines the contribution of key immune pathways to epithelial antimicrobial peptide regulation. Using a murine model of VVC and the virulent C. albicans strain SC5314, we aimed to evaluate the immune signaling pathways governing the temporal regulation of epithelial BD-1 and BD-3 expression during vaginal infection. In wild-type mice, both defensins displayed a biphasic pattern: early induction followed by attenuation as infection progressed. Genetic loss-of-function approaches revealed that NLRP3/IL-1β signaling is required for early BD-1 induction, whereas IL-17RA signaling preferentially supports sustained BD-3 expression. Together, these findings establish a causal and temporal link between host immune signaling and epithelial defensin regulation and reveal a transient subversion of mucosal defenses by C. albicans. This work advances understanding of epithelial innate immunity, defining distinct temporal programs for BD-1 and BD-3 and identifying NLRP3/IL-1β and IL-17RA signaling as key pathways shaping mucosal defensin expression. Full article
(This article belongs to the Special Issue Host–Fungal Interplay: Virulence, Immunity, Antifungal Resistance, and Therapeutic Strategies)
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9 pages, 501 KB  
Communication
Antifungal Susceptibility Testing Experience in the Management of Culture-Positive Mucormycosis: Observation from a Large Healthcare System
by Maryam Naveed, Tirdad T. Zangeneh, Nathan P. Wiederhold, William Lainhart and Mohanad M. Al-Obaidi
J. Fungi 2026, 12(1), 34; https://doi.org/10.3390/jof12010034 - 1 Jan 2026
Cited by 1 | Viewed by 928
Abstract
Background: Mucormycosis, an invasive fungal infection with high morbidity and mortality rates, requires prompt surgical and antifungal therapies; however, the role of antifungal susceptibility testing (AFST) in clinical management of mucormycosis remains underexplored. We aimed to describe the experience of using AFST in [...] Read more.
Background: Mucormycosis, an invasive fungal infection with high morbidity and mortality rates, requires prompt surgical and antifungal therapies; however, the role of antifungal susceptibility testing (AFST) in clinical management of mucormycosis remains underexplored. We aimed to describe the experience of using AFST in the clinical management of mucormycosis. Methods: We conducted a retrospective study from 1 October 2017 to 8 February 2023. We included non-pregnant patients aged ≥ 18 years old with a positive culture for Mucorales and with proven or probable mucormycosis. We collected clinical and microbiological data using a chart review. Results: Over the study period, a total of 119 patients were included, with 36 (30%) undergoing AFST. Of all patients, the median age was 54 years, with 80 (67%) being White and not Hispanic and 73 (61%) being male. Fifty-three (45%) patients had DM, 27 (23%) had hematological malignancy, 15 (13%) had SOT, and 23 (19%) had COVID-19. Half of the cases met the criteria of proven invasive mucormycosis, with pulmonary involvement being the most common presentation (46, 39%), followed by rhino-cerebral-orbital involvement (35, 29%). The majority of Mucorales isolates were Rhizopus species (79, 66%). Among the 36 who underwent AFST, posaconazole minimal inhibitory concentrations (MICs) were lower than isavuconazole (range 0.03 to 2 µg/mL versus 0.1 to 16 µg/mL, respectively). AFST resulted in a change in antifungal therapy from isavuconazole to posaconazole in 3/36 (8%) cases. There was no statistically significant difference in the mortality between the patients whose isolates received AFST versus those who did not have AFST performed. Conclusions: AFST led to a change in antifungal therapy in a minority of mucormycosis cases. Further studies to understand the epidemiological range of antifungal MICs and the effect of AFST-informed antifungal therapy are needed. Full article
(This article belongs to the Special Issue Host–Fungal Interplay: Virulence, Immunity, Antifungal Resistance, and Therapeutic Strategies)
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Review

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22 pages, 421 KB  
Review
From the Ground to the Clinic: The Evolution and Adaptation of Fungi
by Dario Corrêa-Junior, Daniel Zamith-Miranda, Susana Frases and Joshua D. Nosanchuk
J. Fungi 2026, 12(1), 8; https://doi.org/10.3390/jof12010008 - 23 Dec 2025
Cited by 5 | Viewed by 1977
Abstract
Fungi constitute a diverse kingdom of eukaryotic organisms with remarkable adaptability, ranging from saprophytic decomposers to lethal human pathogens. This review synthesizes current insights into fungal adaptations that underline pathogenesis, focusing on enzymatic strategies including hydrolytic enzymes, metabolic and physiological plasticity such as [...] Read more.
Fungi constitute a diverse kingdom of eukaryotic organisms with remarkable adaptability, ranging from saprophytic decomposers to lethal human pathogens. This review synthesizes current insights into fungal adaptations that underline pathogenesis, focusing on enzymatic strategies including hydrolytic enzymes, metabolic and physiological plasticity such as thermotolerance and nutrient flexibility, and evasion of host immunity via mechanisms like melanin production and biofilm formation. We detail fungal survival tactics including spore formation and genomic and epigenetic plasticity, which contribute to resilience and evolution under environmental and host-imposed stresses. The escalating emergence of antifungal resistance and the global impact of environmental changes underscore urgent clinical challenges. Advances in diagnostics, novel therapeutics incorporating AI-assisted drug discovery, and integrated One Health approaches are poised to combat this growing threat. This comprehensive overview aims to guide future research and inform clinical management of fungal infections in an era of dynamic microbial evolution and environmental upheaval. Full article
(This article belongs to the Special Issue Host–Fungal Interplay: Virulence, Immunity, Antifungal Resistance, and Therapeutic Strategies)
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