Six Studies Map Emerging Fungal Pathogens and Their Disease Mechanisms

A new editorial collection published in Frontiers in Cellular and Infection Microbiology brings together six research articles that expand how scientists understand fungal pathogenesis, the molecular machinery by which fungi invade hosts, evade immunity, and drive disease. The collection was assembled by Joseph T. Nickels, Jr of Genesis Biotechnology Group, Yuanwei Zhang of Nanjing Normal University, Scott Gygax of Thomas Jefferson University, and Daniel Henk of the University of Bath. Pathogenic microbes, the editors note, exploit both host and microbial systems to cause disease, hijacking host pathways to enhance their virulence. Virulence therefore emerges not from the fungus alone but from the coordinated activity of complex molecular networks operating on both sides of the host-pathogen interface.

Although Candida albicans and Nakaseomyces glabratus, formerly known as Candida glabrata, remain among the most common fungal pathogens in immunocompromised individuals, other fungal species are increasingly emerging as drivers of disease progression. This shifting landscape of fungal threats is a central theme running through the collection. The six articles span an unusually broad range of topics: the chronological evolution of the literature on sporotrichosis, a fungus linked to autoimmune joint disease in a monkey model, taxonomic reclassification of Candida species and their resistance mechanisms, the description of two new genera of plant-pathogenic fungi, diagnostic risk factors for pediatric pulmonary aspergillosis, and the metabolic roles of virulence kinases in Cryptococcus neoformans. Together, the editors write, these studies are intended to advance knowledge of the fundamental pathogenic processes through which diverse fungal species increase disease burden, morbidity, and mortality in affected individuals.

The first article highlighted in the collection is a comprehensive review by Yuan and colleagues tracing the chronological evolution of the scientific literature on sporotrichosis, an infectious disease caused by the fungus Sporothrix schenckii. Sporotrichosis can occur in immunocompromised individuals, and cases typically present as lymphocutaneous lesions that may progress to open sores or ulcers. When the infection disseminates, it can spread to the lungs, bones, and central nervous system, at which point it becomes life-threatening. By mapping how understanding of the disease has developed over time, Yuan and colleagues identified a need for more definitive research on the mechanisms underlying disease progression, as well as for investigation into therapeutic drug discovery. The authors emphasized that collaborative efforts could accelerate progress toward the development of effective treatments for immunocompromised individuals affected by this deadly disease.

A particularly striking contribution comes from Zhang and colleagues, who isolated the fungus Kazachstania pintolopesii from a monkey model of ankylosing spondylitis, an autoimmune rheumatic disease. Individuals with autoimmune rheumatic diseases are known to be susceptible to microbial infections, and alterations in the host microbiota have been associated with autoimmune disorders. The team demonstrated that K. pintolopesii induces the assembly and activity of PANoptosomes, multiprotein complexes that promote immune cell death through three distinct programmed pathways simultaneously: apoptosis, pyroptosis, and necroptosis. However, the molecular mechanisms underlying this effect remain unclear. The researchers showed that the fungus disrupts immune homeostasis and causes joint disease by activating an immune-endothelial-fibroblast cascade that drives inflammatory cytokine production and fibrosis. Bioinformatic analyses further suggested T-cell activation in osteoblasts.

These findings identify K. pintolopesii as a contributor to autoimmune disease and open new avenues for therapeutic strategies, though the authors caution that future mechanistic studies are needed to define exactly how this fungus activates PANoptosis at the molecular level. The work, conducted in an animal model, adds to a growing body of evidence that fungal organisms can participate in inflammatory and autoimmune processes rather than only in classic opportunistic infection, and it underscores the editorial’s broader argument that fungal contributions to disease extend across multiple biological systems.

A second major thread in the collection concerns the Candida genus, which represents a major health concern by causing morbidity and mortality in immunocompromised individuals, a challenge intensified by the emergence of antifungal-resistant strains. Increased infections caused by emerging Candida species, including C. krusei, C. parapsilosis, C. tropicalis, and C. auris, have been reported in neonatal units, nursing homes for older adults, and patients with cancer. Fernandes and colleagues review the recent literature on Candida species, with particular emphasis on the taxonomic reclassification of these and other clinically relevant fungi, their virulence factors, pathogenic mechanisms, and the molecular basis of antifungal resistance. The review summarizes topics such as biofilm formation and its contribution to antifungal resistance, as well as the role of adhesins in host-pathogen interactions.

The Fernandes review also examines the biology of Candida species and their resistance to the major classes of antifungal agents, including azoles, echinocandins, and polyenes. By consolidating current knowledge of how these organisms are classified, how they attach to and invade host tissue, and how they withstand frontline drugs, the review provides a reference point for researchers working on new antifungal strategies against a genus whose clinical importance continues to grow.

The collection also reaches beyond human medicine. Singh and colleagues expanded the taxonomic nomenclature of cercosporoid hyphomycetous fungi by proposing two new genera within the family Mycosphaerellaceae, a group of fungi that can infect a wide range of plants. Their classification is supported by molecular analyses linked to fungal diversity and pathogenic potential. Using multiple approaches, the authors identified their isolates as novel cercosporoid fungi, providing a refined framework for understanding their taxonomy and evolutionary relationships. The two newly proposed genera are Marcstadlera, represented by the species M. malloti, and Neoclypeosphaerella, represented by N. calotropidis. The two species differ in conidial loci and hila morphology, microscopic features of the spore-producing structures that taxonomists use to distinguish closely related lineages. These findings broaden understanding of pathogenic fungi associated with severe plant diseases.

On the clinical diagnostics front, Yang and colleagues tackled pulmonary aspergillosis, a disease caused by pathogenic Aspergillus species that occurs predominantly in individuals with underlying risk factors or impaired immunity. The disease primarily affects immunocompromised individuals and pediatric patients, and accurate diagnosis remains challenging because pulmonary aspergillosis can be difficult to distinguish from non-aspergillosis respiratory infections. The obstacles are practical as well as biological: overlapping clinical symptoms, difficulties in obtaining appropriate respiratory specimens, and limited availability of diagnostic fungal biomarker tests all complicate diagnosis. In their study, Yang and colleagues identified independent risk factors that may help distinguish pediatric patients with pulmonary aspergillosis from those without this fungal infection, including viral coinfection, absence of fever, and elevated serum β-D-glucan levels. From these variables, the authors constructed a diagnostic framework intended to help physicians diagnose and treat aspergillosis.

The final study in the collection turns to basic molecular biology with drug-discovery implications. Ma and colleagues used integrated proteomic and metabolomic approaches to define the metabolic changes associated with deleting Irk2 or Irk5, infectivity-related kinases that are important virulence determinants in Cryptococcus neoformans infections. These kinases support the ability of C. neoformans to adapt to metabolic environments, making them targets for drug discovery. Proteomic KEGG pathway analysis linked the kinases to pathways regulating carbohydrate, amino acid, and lipid metabolism, while metabolomic profiling implicated them in aminoacyl-tRNA and amino acid biosynthesis. Notably, the team uncovered a potential role for Irk2 and Irk5 in mitochondrial function, observing increased ATP levels in the single-gene deletion strains. These findings suggest that the reduced virulence of the irk2Δ and irk5Δ mutant strains may result from altered mitochondrial oxidative phosphorylation and disrupted ATP homeostasis, linking a fungal energy-management system directly to disease-causing capacity.

In summary, the editors write, this series emphasizes the dynamic and multifaceted interactions between fungal pathogens and their hosts. The articles examine fungal disease biology across several levels, including host immune activation, pathogen-driven inflammatory responses, fungal virulence mechanisms, metabolic adaptation, and mitochondrial function. They highlight the complexity of pathogenesis and identify both gaps in current knowledge and therapeutic opportunities. By integrating insights from clinical observations, experimental models, and systems-level analyses, the collection provides a foundation for research aimed at improving the diagnosis, treatment, and prevention of pathogenic fungal diseases. The editors’ overarching message is that fungal pathogenesis is a multifaceted and evolving field, and that progress will depend on connecting taxonomy, molecular mechanism, metabolism, and clinical practice into a single coherent picture.

Subject of Research: Fungal pathogenesis mechanisms, emerging fungal pathogens, and antifungal resistance

Article Title: Editorial: Perspectives in fungal pathogenesis: 2025

Article References: Nickels, J. T., Jr, Zhang, Y., Gygax, S. E., & Henk, D. (2026). Editorial: Perspectives in fungal pathogenesis: 2025. Frontiers in Cellular and Infection Microbiology, 16, Article 2020473. https://doi.org/10.3389/fcimb.2026.2020473

Image Credits: AI Generated

DOI: 10.3389/fcimb.2026.2020473

Keywords: fungal pathogenesis, Candida, Cryptococcus neoformans, sporotrichosis, aspergillosis, antifungal resistance, PANoptosis, Kazachstania pintolopesii, Mycosphaerellaceae, virulence kinases, immunocompromised, taxonomy