Multidrug-Resistant Fungi, 2nd Edition

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: 31 October 2025 | Viewed by 1972

Special Issue Editor


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Guest Editor
Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Interests: multidrug resistance; fungi; antifungal; efflux pumps; ATPase
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Special Issue Information

Dear Colleagues,

The multidrug resistance (MDR) phenotype is the major factor responsible for the failure of antifungal therapy, increasing the length of hospital stay, treatment’s cost, and death rate. The main mechanisms of antifungal resistance are related to: 1) the presence of transporter proteins in the plasma membrane, extruding drugs from the intracellular milieu and therefore preventing them from reaching the necessary concentration which would allow them to be effective against the fungi; and 2) biofilm production. Nonetheless, other mechanisms may be observed, such as point mutations at ERG11 and FKS. Due to the importance of MDR to public health, the discovery of new molecules able to inhibit efflux transporters and/or disrupt biofilms emerges as a promising strategy for strengthening the antifungal arsenal. This Special Issue aims to feature and promote research regarding drugs that block the multidrug resistance phenotype.

Prof. Dr. Antônio Ferreira-Pereira
Guest Editor

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Keywords

  • antimicrobial resistance
  • efflux pumps
  • multidrug resistance
  • antifungal

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Published Papers (2 papers)

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23 pages, 3511 KiB  
Article
Adaptative Divergence of Cryptococcus neoformans: Phenetic and Metabolomic Profiles Reveal Distinct Pathways of Virulence and Resistance in Clinical vs. Environmental Isolates
by Camila Botelho Miguel, Geovana Pina Vilela, Lara Mamede Almeida, Mariane Andrade Moreira, Glicélia Pereira Silva, Jamil Miguel-Neto, Melissa Carvalho Martins-de-Abreu, Ferdinando Agostinho, Javier Emilio Lazo-Chica, Mariana Santos Cardoso, Siomar de Castro Soares, Aristóteles Góes-Neto and Wellington Francisco Rodrigues
J. Fungi 2025, 11(3), 215; https://doi.org/10.3390/jof11030215 - 12 Mar 2025
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Abstract
Cryptococcus neoformans is a life-threatening fungal pathogen that primarily affects immunocompromised individuals. While antiretroviral therapy has reduced incidence in developed nations, fluconazole-resistant strains and virulent environmental isolates continue to pose challenges, especially because they have many mechanisms of adaptability, supporting their survival. This [...] Read more.
Cryptococcus neoformans is a life-threatening fungal pathogen that primarily affects immunocompromised individuals. While antiretroviral therapy has reduced incidence in developed nations, fluconazole-resistant strains and virulent environmental isolates continue to pose challenges, especially because they have many mechanisms of adaptability, supporting their survival. This study explores the phenetic and metabolomic adaptations of C. neoformans in clinical and environmental contexts to understand the factors influencing pathogenicity and resistance. Methods: An in silico observational study was conducted with 16 C. neoformans isolates (6 clinical, 9 environmental, and 1 reference) from the NCBI database. Molecular phenetic analysis used MEGA version 11.0.13 and focused on efflux pump protein sequences. Molecular phenetic relationships were assessed via the UPGMA clustering method with 1000 bootstrap replicates. The enzymatic profiling of glycolytic pathways was conducted with dbCAN, and metabolomic pathway enrichment analysis was performed in MetaboAnalyst 6.0 using the KEGG pathway database. Results: Molecular phenetic analysis revealed distinct clustering patterns among isolates, reflecting adaptations associated with clinical and environmental niches. Clinical isolates demonstrated enriched sulfur metabolism and glutathione pathways, likely adaptations to oxidative stress in host environments, while environmental isolates favored methane and glyoxylate pathways, suggesting adaptations for survival in carbon-rich environments. Conclusion: Significant phenetic and metabolomic distinctions between isolates reveal adaptive strategies for enhancing virulence and antifungal resistance, highlighting potential therapeutic targets. Full article
(This article belongs to the Special Issue Multidrug-Resistant Fungi, 2nd Edition)
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Brief Report
The Heterogenous Presentation of Hepatic Mucormycosis in Adults: A Case Report and Review of the Literature
by Hazim Allos, Rachel S. Hicklen, Takahiro Matsuo, Javier Adachi, Sebastian Wurster and Dimitrios P. Kontoyiannis
J. Fungi 2025, 11(6), 408; https://doi.org/10.3390/jof11060408 - 26 May 2025
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Abstract
Hepatic mucormycosis is a rare but often fatal opportunistic fungal infection, primarily affecting immunocompromised patients. Herein, we report such a case from MD Anderson Cancer Center (Houston, TX, USA) and systematically review published cases in patients ≥ 19 years of age to better [...] Read more.
Hepatic mucormycosis is a rare but often fatal opportunistic fungal infection, primarily affecting immunocompromised patients. Herein, we report such a case from MD Anderson Cancer Center (Houston, TX, USA) and systematically review published cases in patients ≥ 19 years of age to better characterize clinical presentation, diagnostic challenges, and treatment outcomes of hepatic mucormycosis. Among the 40 identified cases (including ours), hematologic malignancies (55%) and solid organ transplantation (30%) were the most common underlying conditions. Fever (70%) and abdominal pain (63%) were the predominant symptoms. Imaging revealed multiple hepatic lesions in 72% of cases. Diagnosis was primarily based on histopathology (73%), whereas culture positivity was low (36%), underscoring the difficulty of pathogen isolation. Mucorales-active antifungal therapy was often delayed but eventually used in 85% of cases (all amphotericin B +/− Mucorales-active triazoles), while 45% underwent additional surgical intervention. Despite treatment, 1-year all-cause mortality remained high at 46%, with a trend towards lower mortality for those who underwent surgery compared to non-surgical management (35% vs. 55%, p = 0.334). These findings highlight the aggressive nature of hepatic mucormycosis and the importance of early recognition as well as the need for non-culture-based diagnostics and multimodal treatment approaches. Improved awareness and further research into optimized management strategies are crucial to improve the outcomes of this challenging infection. Full article
(This article belongs to the Special Issue Multidrug-Resistant Fungi, 2nd Edition)
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