The major fungal pathogen, Candida albicans, exists as a commensal in the gastrointestinal tract of healthy humans. Fungal colonisation levels increase during gut dysbiosis, when the local microbiota and short-chain fatty acid (SCFA) concentrations become perturbed. Individually, acetic, propionic and butyric acids are reported to exert differential effects on C.
View Article and Find Full Text PDFInvasive candidiasis affects 1.6 million people annually, with high mortality among immunocompromised and hospitalized patients. Echinocandins are frontline antifungals, but rising resistance limits their efficacy.
View Article and Find Full Text PDFChitosan, the deacetylated product of chitin, is a significant component of the cell walls of nearly all fungi. In contrast with the high level of attention paid to plant immune recognition of chitin and chitosan of plant pathogenic fungi we know much less about the mammalian immune system immune recognition of chitosan during infections by human pathogenic fungal species. Here we show that the mammalian β-integrin CR3 complement scavenger receptor, that is expressed on monocytes and macrophages, recognises chitosan from a range of fungal sources and that this leads to the secretion of IL-6, IL-1β and TNF.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2025
Fungal pathogens infect billions and kill millions of people each year. Many of these pathogens have evolved strategies to evade our antifungal immune defenses. for example, masks the proinflammatory pathogen-associated molecular pattern (PAMP) β-1,3-glucan, in response to specific host signals such as lactate.
View Article and Find Full Text PDFClinical isolates of Candida auris show a high prevalence of resistance to Amphotericin B (AmB)-an uncommon trait in most Candida species. Alterations in ergosterol biosynthesis can contribute to acquired AmB resistance in C. auris laboratory strains but are rarely seen in clinical isolates.
View Article and Find Full Text PDFFungal Genet Biol
June 2025
The cell wall is the defining organelle of filamentous and yeast-like fungi. It is responsible for morphology, biotic and abiotic interactions and its components confer its unique and variable signature, making it a natural target for antifungal drugs, but a moving target for immune recognition. The wall is however more than the sum of its many parts.
View Article and Find Full Text PDFNat Microbiol
April 2025
Since their discovery in 2007, there has been growing awareness of the importance of fungal extracellular vesicles (EVs) for fungal physiology, host-pathogen interactions and virulence. Fungal EVs are nanostructures comprising bilayered membranes and molecules of various types that participate in several pathophysiological processes in fungal biology, including secretion, cellular communication, immunopathogenesis and drug resistance. However, many questions remain regarding the classification of EVs, their cellular origin, passage across the cell wall, experimental models for functional and compositional analyses, production in vitro and in vivo and biomarkers for EVs.
View Article and Find Full Text PDFIntroduction: Chitin is a highly abundant polysaccharide in nature and is linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent inmammals and plants and, thus, represents a microbeassociatedmolecular pattern (MAMP). However, highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors.
View Article and Find Full Text PDFOver the past billion years, the fungal kingdom has diversified to more than two million species, with over 95% still undescribed. Beyond the well-known macroscopic mushrooms and microscopic yeast, fungi are heterotrophs that feed on almost any organic carbon, recycling nutrients through the decay of dead plants and animals and sequestering carbon into Earth's ecosystems. Human-directed applications of fungi extend from leavened bread, alcoholic beverages and biofuels to pharmaceuticals, including antibiotics and psychoactive compounds.
View Article and Find Full Text PDFVirulence
December 2025
Vulvovaginal candidiasis (VVC) is one of the most common infections caused by . VVC is characterized by an inadequate hyperinflammatory response and clinical symptoms associated with colonization of the vaginal mucosa. Compared to other host niches in which can cause infection, the vaginal environment is extremely rich in lactic acid that is produced by the vaginal microbiota.
View Article and Find Full Text PDFThe cell wall of human fungal pathogens plays critical roles as an architectural scaffold and as a target and modulator of the host immune response. Although the cell wall of the pathogenic yeast is intensively studied, one of the major fibrillar components in its cell wall, β-1,6-glucan, has been largely neglected. Here, we show that β-1,6-glucan is essential for bilayered cell wall organization, cell wall integrity, and filamentous growth.
View Article and Find Full Text PDFThe fungal community of the skin microbiome is dominated by a single genus, Malassezia. Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity.
View Article and Find Full Text PDFNPJ Antimicrob Resist
November 2024
The emergence of fungal antimicrobial resistance-fAMR-is having a growing impact on human and animal health, and food security. This roadmap charts inter-related actions that will enhance our ability to mitigate the risk of fAMR. As humanity's reliance on antifungal chemicals escalates, our understanding of their one-health consequences needs to scale accordingly if we are to protect our ability to manage the global spectrum of fungal disease sustainably.
View Article and Find Full Text PDFInvasive candidiasis and candidemia remain a significant public health concern. The European Confederation of Medical Mycology (ECMM) conducted three pan-European multicentre studies from 1997 to 2022 to investigate various aspects of invasive Candida infections. These studies revealed shifting trends in Candida species distribution, with an increase of non-albicans Candida species as causative pathogens, increasing rates of antifungal resistance, and persistently high mortality rates.
View Article and Find Full Text PDFThe fungal community of the skin microbiome is dominated by a single genus, . Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity.
View Article and Find Full Text PDFmSphere
August 2024
Systemic candidiasis remains a significant public health concern worldwide, with high mortality rates despite available antifungal drugs. Drug-resistant strains add to the urgency for alternative therapies. In this context, vaccination has reemerged as a prominent immune-based strategy.
View Article and Find Full Text PDFHost recognition of the pathogen-associated molecular pattern (PAMP), β-1,3-glucan, plays a major role in antifungal immunity. β-1,3-glucan is an essential component of the inner cell wall of the opportunistic pathogen . Most β-1,3-glucan is shielded by the outer cell wall layer of mannan fibrils, but some can become exposed at the cell surface.
View Article and Find Full Text PDFNat Rev Microbiol
November 2024
Microbiol Mol Biol Rev
June 2024
SUMMARYA significant increase in the incidence of -mediated infections has been observed in the last decade, mainly due to rising numbers of susceptible individuals. Recently, the World Health Organization published its first fungal pathogen priority list, with species listed in medium, high, and critical priority categories. This review is a synthesis of information and recent advances in our understanding of two of these species and .
View Article and Find Full Text PDFJ Infect Dis
September 2024
The interaction between the Candida albicans cell wall and pattern recognition receptors is crucial for the initiation of host immune responses, which, ultimately, contribute to the clearance of this pathogenic fungus. In the present study, we investigate the ability of C. albicans mannans to modulate immune response and induce innate immune memory (also termed trained immunity).
View Article and Find Full Text PDFMicrobial species capable of co-existing with healthy individuals, such as the commensal fungus exploit multifarious strategies to evade our immune defenses. These strategies include the masking of immunoinflammatory pathogen-associated molecular patterns (PAMPs) at their cell surface. We reported previously that actively reduces the exposure of the proinflammatory PAMP, β-1,3-glucan, at its cell surface in response to host-related signals such as lactate and hypoxia.
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