Featured
-
-
Article
| Open AccessLarge-scale identification of genes involved in septal pore plugging in multicellular fungi
Multicellular fungi have septal pores that allow cytoplasmic exchange between adjacent cells; cell wounding and other stress conditions induce septal pore closure. Here, Mamun et al. determine the subcellular localization of hundreds of uncharacterized proteins in a multicellular fungus, identifying 62 proteins associated with the septum. Of these, 23 proteins are involved in septal pore plugging upon hyphal wounding.
- Md. Abdulla Al Mamun
- , Wei Cao
- & Jun-ichi Maruyama
-
Article
| Open AccessMacrophage internalization creates a multidrug-tolerant fungal persister reservoir and facilitates the emergence of drug resistance
Arastehfar et al. show that macrophage-engulfed cells of fungal pathogen Candida glabrata exhibit multidrug tolerance and increased survival in the presence of cidal antifungal drugs, forming a reservoir from which drug-resistant mutants emerge
- Amir Arastehfar
- , Farnaz Daneshnia
- & David S. Perlin
-
Article
| Open AccessReciprocal modulation of ammonia and melanin production has implications for cryptococcal virulence
Cryptococcus neoformans has numerous described virulence mechanisms including urease secretion and melanization. Here, Baker and Casadevall, describe the reciprocal relationship between these two factors and their contribution to infection.
- Rosanna P. Baker
- & Arturo Casadevall
-
Article
| Open AccessRegulatory basis for reproductive flexibility in a meningitis-causing fungal pathogen
Pathogenic fungi of the genus Cryptococcus can undergo bisexual and unisexual reproduction. Here, the authors construct a gene-deletion library for over 100 transcription factor genes in Cryptococcus deneoformans and provide insights into regulatory cascades that are specific for each reproductive mode.
- Pengjie Hu
- , Hao Ding
- & Linqi Wang
-
Article
| Open AccessCRISPR-Cas12a induced DNA double-strand breaks are repaired by multiple pathways with different mutation profiles in Magnaporthe oryzae
In this work, Huang and colleagues describe variation in DNA repair outcomes due to distinct repair mechanisms following CRISPR targeting of different loci in the plant pathogenic fungus Magnaporthe oryzae.
- Jun Huang
- , David Rowe
- & David E. Cook
-
Article
| Open AccessPD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow
Programmed death ligand 1 (PD-L1) suppresses host immunity during infection and microbial sepsis. Here, the authors show that PD-L1 does this by regulating the secretion of CXCL1 and CXCL2 to control neutrophil mobilization during Candida albicans infection.
- Yao Yu
- , Rong-Rong Wang
- & Xin-Ming Jia
-
Article
| Open AccessUbiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans
The pathogenic yeast Cryptococcus neoformans forms large, so-called ‘titan cells’ during infection. Here, Cao et al. show that a ubiquitin ligase inhibits this process by targeting for degradation a CDK-related kinase that stimulates titan cell formation.
- Chengjun Cao
- , Keyi Wang
- & Chaoyang Xue
-
Article
| Open AccessProteome effects of genome-wide single gene perturbations
Protein abundance is controlled at the transcriptional, translational and posttranslational levels. Here, Öztürk et al. determine proteome changes resulting from individual knockout of 3308 nonessential genes in the yeast S. pombe, infer gene functionality, and show that protein upregulation under stable transcript expression utilizes optimal codons.
- Merve Öztürk
- , Anja Freiwald
- & Falk Butter
-
Article
| Open AccessStructural and functional analysis of EntV reveals a 12 amino acid fragment protective against fungal infections
Enterococcus faecalis has been reported to inhibit Candida albicans virulence via secretion of the bacteriocin EntV. Here, the authors present the crystal structure and characterise the antifungal properties of this peptide in numerous in vitro and in vivo assays.
- Melissa R. Cruz
- , Shane Cristy
- & Danielle A. Garsin
-
Article
| Open AccessZymoseptoria tritici white-collar complex integrates light, temperature and plant cues to initiate dimorphism and pathogenesis
Transitioning from spores to hyphae is crucial for host invasion by the plant pathogenic fungus Zymoseptoria tritici. Here, the authors show that the spore-to-hypha transition is enhanced by wheat leaf surface compounds and is regulated by the white-collar complex, which integrates light with biotic and abiotic cues to allow host invasion through open stomata.
- Sreedhar Kilaru
- , Elena Fantozzi
- & Gero Steinberg
-
Article
| Open AccessIL-23 signaling prevents ferroptosis-driven renal immunopathology during candidiasis
The beta-glucan receptor EphA2 is known to maintain mucosal immunity. Here, its role in modulating renal immunopathology via IL-23 signalling and ferroptotic cell death during candidiasis is characterised.
- Nicolas Millet
- , Norma V. Solis
- & Marc Swidergall
-
Article
| Open AccessCryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process
Mitochondrial quality control prevents accumulation of intramitochondrial reactive oxygen species (mtROS), thus protecting cells against DNA damage. Here, Gao et al. show that an atypical heat shock factor responds to intramitochondrial stresses and regulates mtROS homeostasis in the pathogenic fungus Cryptococcus neoformans.
- Xindi Gao
- , Yi Fu
- & Chen Ding
-
Article
| Open AccessTelomere-to-telomere genome sequence of the model mould pathogen Aspergillus fumigatus
The fungus Aspergillus fumigatus causes invasive and chronic diseases worldwide. Here, Bowyer et al. use long-read and short-read sequencing to generate complete chromosome assemblies and telomere-to-telomere coverage for two isolates, thus providing high-quality reference genomes as fundamental resources to study this pathogen.
- Paul Bowyer
- , Andrew Currin
- & Marcin G. Fraczek
-
Review Article
| Open AccessThe importance of antimicrobial resistance in medical mycology
The impact of fungal infections on human health has been exacerbated by the rise of antifungal drug resistance. In this Review, the authors outline the problem of antifungal resistance and suggest how this growing threat might be mitigated.
- Neil A. R. Gow
- , Carolyn Johnson
- & Keegan Edgar
-
Article
| Open AccessCopper starvation induces antimicrobial isocyanide integrated into two distinct biosynthetic pathways in fungi
The genomes of filamentous fungi, such as Aspergillus, include many biosynthetic gene clusters of unknown function. Here, the authors show that copper starvation induces expression of an enzyme that generates a valine-derived isocyanide participating in two different pathways, for biosynthesis of acylated sugar alcohols and modified ergot alkaloids.
- Tae Hyung Won
- , Jin Woo Bok
- & Frank C. Schroeder
-
Article
| Open AccessGlobal genomic analyses of wheat powdery mildew reveal association of pathogen spread with historical human migration and trade
The fungus Blumeria graminis f. sp. tritici causes wheat powdery mildew disease. Here, Sotiropoulos et al. analyze a global sample of 172 mildew genomes, providing evidence that humans drove global spread of the pathogen throughout history and that mildew rapidly evolved through hybridization with local fungal strains.
- Alexandros G. Sotiropoulos
- , Epifanía Arango-Isaza
- & Thomas Wicker
-
Article
| Open AccessA phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans
Chromosomal instability caused by cell division errors is associated with antifungal drug resistance in fungal pathogens. Here, Jaitly et al. identify several genes involved in chromosomal stability in Candida albicans, including a phylogenetically restricted gene encoding an essential cell-cycle progression factor.
- Priya Jaitly
- , Mélanie Legrand
- & Kaustuv Sanyal
-
Article
| Open AccessInhibition of myeloid-derived suppressor cell arginase-1 production enhances T-cell-based immunotherapy against Cryptococcus neoformans infection
Cryptococcus neoformans causes opportunistic infection and potentially lethal immunopathology but therapeutic options are limited. Here the authors implicate myeloid derived suppressor cells during C. neoformans infection and suggest targeting arginase-1 production as a potential therapeutic strategy.
- Ya-Nan Li
- , Zhong-Wei Wang
- & Xin-Ming Jia
-
Article
| Open AccessTrans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage
The fungal pathogen Candida albicans forms filamentous hyphae that can invade the epithelium. Here, Lachat et al. show that C. albicans early invasion of epithelial tissues can lead to either host membrane breaching and host cell death, or trans-cellular tunnelling through host cells without membrane breaching.
- Joy Lachat
- , Alice Pascault
- & Allon Weiner
-
Article
| Open AccessTargeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation
There is an urgent need for novel strategies to combat life-threatening fungal infections. Here, Revie et al. identify a compound that induces alterations in fungal membranes, synergizes with azole antifungals against the pathogen Candida albicans, and inhibits virulence traits and biofilm formation in animal models of infection.
- Nicole M. Revie
- , Kali R. Iyer
- & Leah E. Cowen
-
Article
| Open AccessHigh-resolution mass measurements of single budding yeast reveal linear growth segments
Measuring the mass of individual microbial cells remains challenging. Here, the authors present a cell balance to monitor the proliferation of single budding yeast cells under culture conditions in real time, showing that single cells increase total mass in multiple linear segments of constant growth rates.
- Andreas P. Cuny
- , K. Tanuj Sapra
- & Daniel J. Müller
-
Article
| Open AccessInnate immune responses against the fungal pathogen Candida auris
Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Here, the authors identify differential innate immune responses induced by C. auris and Candida albicans in vitro and in vivo, which correlate with structural features of the cell wall.
- Yuanyuan Wang
- , Yun Zou
- & Dongsheng Zhou
-
Article
| Open AccessLactobacillus rhamnosus colonisation antagonizes Candida albicans by forcing metabolic adaptations that compromise pathogenicity
Commensal bacteria such as Lactobacillus rhamnosus can inhibit the pathogenicity of the fungus Candida albicans. Here, Alonso-Roman et al. investigate the interplay between C. albicans, L. rhamnosus and intestinal epithelial cells, showing that changes in the metabolic environment, induced by the bacteria, trigger adaptations in C. albicans that reduce fungal pathogenicity.
- Raquel Alonso-Roman
- , Antonia Last
- & Mark S. Gresnigt
-
Article
| Open AccessTemporal changes in gastrointestinal fungi and the risk of autoimmunity during early childhood: the TEDDY study
Here, via metagenomics and ITS2 sequencing analysis of children's stool samples from three months to four years, the authors show that the fungal composition changes and relative abundance increases at weaning, but unlike bacteria, the overall levels of fungal diversity do not change substantially over time.
- Thomas A. Auchtung
- , Christopher J. Stewart
- & Joseph F. Petrosino
-
Article
| Open AccessLarge differences in carbohydrate degradation and transport potential among lichen fungal symbionts
Lichen symbioses are thought to be stabilized by the transfer of fixed carbon from a photosynthesizing symbiont to a fungus. Here, Resl et al. show that, contrary to other fungal symbioses, fungal association with a phototroph in lichens does not result in loss of fungal enzymes for plant cell-wall degradation.
- Philipp Resl
- , Adina R. Bujold
- & Toby Spribille
-
Article
| Open AccessCandida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT
Natural killer cells have emerged as critical immune cells in the response to fungal infection. Here the authors identify how Candida albicans evades the natural killer cell response via expression of ligands that directly modify the natural killer cell response and can be therapeutically targeted to restore the anti-Candida immunity.
- Yoav Charpak-Amikam
- , Tom Lapidus
- & Ofer Mandelboim
-
Article
| Open AccessA fungal extracellular effector inactivates plant polygalacturonase-inhibiting protein
Plants produce polygalacuturonase-inhibiting proteins (PGIPs) to counteract cell wall degradation by pathogenic microbes. Here the authors show that Sclerotinia sclerotiorum, a fungal pathogen that causes stem rot disease, secretes a PGIP-inactivating effector to diminish plant resistance.
- Wei Wei
- , Liangsheng Xu
- & Weidong Chen
-
Article
| Open AccessSWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes
The Pleiotropic Drug Resistance (PDR) network is central to drug response in fungi, and its overactivation is associated with drug resistance. Here the authors show that the chromatin remodeller SWI/SNF and the histone chaperone Rtt106 are important for PDR gene expression in fungi and therefore mediate resistance to antifungal drugs.
- Vladislav N. Nikolov
- , Dhara Malavia
- & Takashi Kubota
-
Article
| Open AccessIn vivo imaging of invasive aspergillosis with 18F-fluorodeoxysorbitol positron emission tomography
Current diagnostic methods for invasive aspergillosis are time-consuming and poorly sensitive. Here, the authors show that positron emission tomography with 2-deoxy-2-18F-fluorosorbitol can visualize Aspergillus fumigatus infection of the lungs, brain and muscles in mouse models, and can distinguish pulmonary aspergillosis from other diseases such as Staphylococcus aureus infection and lung cancer.
- Dong-Yeon Kim
- , Ayoung Pyo
- & Jung-Joon Min
-
Article
| Open AccessThe long non-coding RNA landscape of Candida yeast pathogens
Long non-coding RNAs (lncRNAs) play roles in key cellular processes, but remain largely unexplored in fungal pathogens such as Candida. Here, Hovhannisyan and Gabaldón analyze thousands of sequencing datasets to infer and characterize the lncRNA repertoires of five Candida species, paving the way for their future functional characterization.
- Hrant Hovhannisyan
- & Toni Gabaldón
-
Article
| Open AccessForward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains
Some isolates of the emerging fungal pathogen Candida auris can form cellular aggregates or filaments. Here, Santana and O’Meara use Agrobacterium-mediated transformation and a CRISPR-Cas9 system to identify several genes that regulate C. auris morphogenesis.
- Darian J. Santana
- & Teresa R. O’Meara
-
Article
| Open AccessGenetic determinants of endophytism in the Arabidopsis root mycobiome
Plant roots host diverse fungal communities that affect plant health. Here, Mesny et al. use comparative genomics and transcriptomics of fungal isolates from the Arabidopsis thaliana root mycobiota, together with root colonization assays, to identify genetic determinants of endophytism.
- Fantin Mesny
- , Shingo Miyauchi
- & Stéphane Hacquard
-
Article
| Open AccessDiversity, multifaceted evolution, and facultative saprotrophism in the European Batrachochytrium salamandrivorans epidemic
B. salamandrivorans (Bsal) is a fungus of amphibians that has been implicated in the collapse of salamander populations. Here, the authors sequence nine Bsal isolates from six epidemic sites and describe variation in genome size and composition.
- Moira Kelly
- , Frank Pasmans
- & An Martel
-
Article
| Open AccessLeveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets
The analysis of essential genes in pathogens can be used to discover potential antimicrobial targets. Here, the authors use a machine learning model and chemogenomic analyses to generate genome-wide gene essentiality predictions for the fungal pathogen Candida albicans, define the function of three uncharacterized essential genes, and identify the target of a new antifungal compound.
- Ci Fu
- , Xiang Zhang
- & Leah E. Cowen
-
Article
| Open AccessStructure and activation mechanism of the hexameric plasma membrane H+-ATPase
The plasma membrane H+ -ATPase is responsible for maintenance of the plasma membrane potential, which provides energy for the transport of nutrients, and the plasma membrane H+ -ATPase in S. cerevisiae (Pma1) is a P3A-type ATPase that assembles and functions as a hexamer. Here, the authors present the cryo-EM structures of autoinhibited and activated native Pma1 hexamers purified with endogenous lipids and they propose a mechanism for proton pumping across the membrane by this family of H+ -ATPases.
- Peng Zhao
- , Chaoran Zhao
- & Lin Bai
-
Article
| Open AccessA molecular vision of fungal cell wall organization by functional genomics and solid-state NMR
The fungal cell wall is a complex structure composed mainly of glucans, chitin and glycoproteins. Here, the authors use solid-state NMR spectroscopy to assess the cell wall architecture of Aspergillus fumigatus, comparing wild-type cells and mutants lacking major structural polysaccharides, with insights into the distinct functions of these components.
- Arnab Chakraborty
- , Liyanage D. Fernando
- & Tuo Wang
-
Article
| Open AccessCoordination of fungal biofilm development by extracellular vesicle cargo
The fungal pathogen Candida albicans can release extracellular vesicles that promote biofilm formation and antifungal resistance. Here, Zarnowski et al. define functions for numerous vesicle cargo proteins in biofilm matrix assembly and drug resistance, as well as in fungal cell adhesion and dissemination.
- Robert Zarnowski
- , Andrea Noll
- & David R. Andes
-
Article
| Open AccessA small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase
Alterations of the mucosal microbiota, including Lactobacillus bacteria, are associated with infections caused by the fungus Candida albicans. Here, MacAlpine et al. show that some Lactobacillus strains produce a small molecule that blocks C. albicans filamentation and biofilm formation, and thus virulence, through inhibition of a fungal kinase.
- Jessie MacAlpine
- , Martin Daniel-Ivad
- & Leah E. Cowen
-
Article
| Open AccessThe δ subunit of F1Fo-ATP synthase is required for pathogenicity of Candida albicans
F1Fo-ATP synthase is a key enzyme for energy production in fungi. Here, the authors show that the δ subunit of the enzyme is required for Candida albicans lethal infection and represents a potential therapeutic target.
- Shuixiu Li
- , Yajing Zhao
- & Hong Zhang
-
Article
| Open AccessStructure and inhibition of Cryptococcus neoformans sterylglucosidase to develop antifungal agents
Sterylglucosidase 1 (Sgl1) is a virulence factor in Cryptococcus neoformans that modulates fungal pathogenesis and host response. Here, the authors characterize Sgl1 structurally, identify Sgl1 inhibitors, and demonstrate Sgl1 inhibition has efficacy in mouse models of infection.
- Nivea Pereira de Sa
- , Adam Taouil
- & Michael V. Airola
-
Article
| Open AccessEpidermal galactose spurs chytrid virulence and predicts amphibian colonization
The skin disease chytridiomycosis is linked to global amphibian declines but effective mitigation measures require improved understanding of the mechanisms underpinning the disease ecology. This study identifies key mediators of interactions between the fungal pathogen and amphibian skin, providing a marker of host colonization that can predict susceptibility between amphibian species.
- Yu Wang
- , Elin Verbrugghe
- & An Martel
-
Article
| Open AccessFatal attraction of Caenorhabditis elegans to predatory fungi through 6-methyl-salicylic acid
Methyl salicylate ester is a plant metabolite involved in plant-insect and plant-plant interactions. Here, Yu et al. show that a nematode-trapping fungus has potential to produce a related compound, 6-methyl salicylate, which attracts its prey (nematodes) and modulates spore germination and trap formation in the fungus.
- Xi Yu
- , Xiaodi Hu
- & Reinhard Fischer
-
Article
| Open AccessChanges in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation
Analyses of both natural and experimental evolution suggest that adaptation depends on the evolutionary past and adaptive potential decreases over time. Here, by tracking yeast adaptation with DNA barcoding, the authors show that such evolutionary phenomena can be observed even after a single adaptive step.
- Dimitra Aggeli
- , Yuping Li
- & Gavin Sherlock
-
Article
| Open AccessPhylogenomics of a new fungal phylum reveals multiple waves of reductive evolution across Holomycota
Unicellular fungi with free-living flagellated stages (zoospores) remain poorly known. Here, Galindo et al. sequence single-cell genomes for two atypical parasitic fungi with amoeboid zoospores, and re-evaluate the branching order of early-diverging fungi and the evolution of fungal multicellularity and flagellum-mediated motility.
- Luis Javier Galindo
- , Purificación López-García
- & David Moreira
-
Article
| Open AccessRapid proliferation due to better metabolic adaptation results in full virulence of a filament-deficient Candida albicans strain
The ability of the fungal pathogen Candida albicans to undergo yeast-to-hypha transition is believed to be a key virulence factor. Here, Dunker et al. show that a filament-deficient strain is attenuated in a mouse model of intraperitoneal infection, but remains virulent in a mouse model of systemic candidiasis.
- Christine Dunker
- , Melanie Polke
- & Ilse D. Jacobsen
-
Article
| Open AccessMachine-learning predicts genomic determinants of meiosis-driven structural variation in a eukaryotic pathogen
Structural variation in genomes of the same species is frequent but what drives the rearrangements remains unclear. Machine-learning of rearrangement patterns among telomere-to-telomere assemblies can accurately identify regions of intrinsic DNA instability in a eukaryotic pathogen.
- Thomas Badet
- , Simone Fouché
- & Daniel Croll
-
Article
| Open AccessModerate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci
Pathogenic fungi rapidly develop resistance to the antifungal agent 5-fluorocytosine (5-FC). Here, Chang et al. explore the mechanisms by which Cryptococcus develops 5-FC resistance at a high frequency, including mutations in several genes and altered levels of key metabolites.
- Yun C. Chang
- , Ami Khanal Lamichhane
- & Kyung J. Kwon-Chung
-
Article
| Open AccessThe RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium
Human RBM42 associates with the spliceosome complex. Here the authors show that the fungus counterpart of RBM42, FgRbp1 regulates splicing by interacting with FgU2AF23.
- Minhui Wang
- , Tianling Ma
- & Zhonghua Ma
-
Article
| Open AccessA peptidoglycan storm caused by β-lactam antibiotic’s action on host microbiota drives Candida albicans infection
A risk factor for invasive Candida albicans infection is the use of broad-spectrum antibiotics, but the reasons are poorly understood. Here, the authors show in mice that β-lactam antibiotics cause commensal bacteria to release peptidoglycan fragments that induce the invasive hyphal growth of C. albicans, leading to systemic dissemination.
- Chew Teng Tan
- , Xiaoli Xu
- & Yue Wang