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Unveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi
A-to-I editing in animals is catalyzed by enzymes of the Adenosine Deaminase Acting on RNA family, orthologues of which do not exist in fungi. Here, Feng et al. characterise the enzymes involved in A-to-I mRNA editing in Fusarium graminearum.
- Chanjing Feng
- , Kaiyun Xin
- & Huiquan Liu
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| Open Access
An oxylipin signal confers protection against antifungal echinocandins in pathogenic aspergilli
Echinocandins are antifungal drugs that inhibit hyphal growth and induce lysis of hyphal tip compartments in pathogenic Aspergillus species. Here, Calise et al. show that echinocandins induce production of a fungal oxylipin signal, thus triggering hyphal growth changes that reduce hyphal tip lysis and confer echinocandin tolerance.
- Dante G. Calise
- , Sung Chul Park
- & Nancy P. Keller
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A secondary mechanism of action for triazole antifungals in Aspergillus fumigatus mediated by hmg1
Triazole antifungals are widely used and exert their action by inhibiting ergosterol biosynthesis. Here, Rybak et al show that these drugs both inhibit ergosterol biosynthesis and induce accumulation of pathway intermediates that directly induce inhibition of sterol synthesis.
- Jeffrey M. Rybak
- , Jinhong Xie
- & Jarrod R. Fortwendel
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Towards establishing a fungal economics spectrum in soil saprobic fungi
Challenges in obtaining empirical trait data hinder the development of trait-based frameworks for soil microbes. Here, the authors analyse traits of saprobic fungal isolates from a grassland site to propose a fungal economics spectrum, suggesting a general trait framework for soil fungi.
- Tessa Camenzind
- , Carlos A. Aguilar-Trigueros
- & Matthias C. Rillig
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Epidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil
Coccidioidomycosis, a WHO-listed mycosis, is neglected in South America. Analysis of 292 cases in Brazil, often tied to armadillo hunting, unveils unique disease patterns, environmental factors and pathogen genetics causing the disease.
- Kelsen Dantas Eulálio
- , Daniel R. Kollath
- & Marcus de Melo Teixeira
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Anaerobic fungi in the tortoise alimentary tract illuminate early stages of host-fungal symbiosis and Neocallimastigomycota evolution
Here, Pratt et al identify a community of deep-branching anaerobic fungi in tortoise feces. Multiple characteristics underpinning their success in tortoise, as opposed to scarcity in mammalian alimentary tracts, are presented.
- Carrie J. Pratt
- , Casey H. Meili
- & Noha H. Youssef
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Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection
Bing et al. report that Candida auris undergoes rapid evolution via de novo genetic mutations and forms multicellular aggregates that exhibit a survival advantage over the single-celled yeast-form phenotype during host infection.
- Jian Bing
- , Zhangyue Guan
- & Guanghua Huang
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Edible mycelium bioengineered for enhanced nutritional value and sensory appeal using a modular synthetic biology toolkit
Fungi have the potential to produce sustainable foods for a growing population, but current products are based on a small number of strains with inherent limitations. Here, the authors develop genetic tools for an edible fungus and engineer its nutritional value and sensory appeal for alternative meat applications.
- Vayu Maini Rekdal
- , Casper R. B. van der Luijt
- & Jay D. Keasling
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Global fungal-host interactome mapping identifies host targets of candidalysin
Candidalysin is a toxin secreted by Candida albicans. Although critical for pathogenesis, its intracellular targets are not well mapped. Here, Zhang et al screen for interacting proteins and identify that candidalysin can modulate the DNA damage repair pathway to promote fungal infection.
- Tian-Yi Zhang
- , Yao-Qi Chen
- & Ning-Ning Liu
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Implications of the three-dimensional chromatin organization for genome evolution in a fungal plant pathogen
The spatial organization of eukaryotic genomes is linked to their biological functions. Here, the authors study the 3D genome organization of the phytopathogenic fungus Verticillium dahliae, revealing links to evolutionary features conserved throughout the Verticillium genus.
- David E. Torres
- , H. Martin Kramer
- & Bart P. H. J. Thomma
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Regulation of TRI5 expression and deoxynivalenol biosynthesis by a long non-coding RNA in Fusarium graminearum
The fungus Fusarium graminearum produces a toxin, deoxynivalenol (DON), that can be found in cereal grains and processed food or feed. Here, Huang et al. study the regulation of DON biosynthesis and show that transcription factors TRI6 and TRI10 regulate each other’s expression and that of a long non-coding RNA which, in turn, downregulates a DON biosynthesis gene.
- Panpan Huang
- , Xiao Yu
- & Cong Jiang
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Cross-feeding promotes heterogeneity within yeast cell populations
Cellular heterogeneity in cell populations of isogenic origin is driven by diverse factors such as nutrient availability and interactions with neighbouring cells. Here, Hu et al. study plasmid retention dynamics in yeast populations, and show that the exchange of complementary metabolites between plasmid-carrying prototrophs and plasmid-free auxotrophs allows the latter to proliferate in selective environments.
- Kevin K. Y. Hu
- , Ankita Suri
- & Victoria S. Haritos
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Temporally-coordinated bivalent histone modifications of BCG1 enable fungal invasion and immune evasion
Bivalent histone modifications control various cellular processes in eukaryotes. Here, the authors report that a fungal pathogen deploys bivalent histone modification to fine-tune the expression of BCG1, thereby facilitating successful infection and host immunity evasion.
- Xiaozhen Zhao
- , Yiming Wang
- & Qin Gu
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Tandem gene duplications contributed to high-level azole resistance in a rapidly expanding Candida tropicalis population
Candida tropicalis is a cause of invasive candidiasis infection in humans that has been increasingly associated with azole drug resistance. In this study, the authors investigate the genetic basis for azole resistance through analysis of whole-genome sequencing and multilocus sequence typing data.
- Xin Fan
- , Rong-Chen Dai
- & Meng Xiao
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A palisade-shaped membrane reservoir is required for rapid ring cell inflation in Drechslerella dactyloides
Nematode trapping fungi must be able to quickly respond to catch nematodes. Here, Chen et al show that the constriction of ring cells in Drechslerella dactyloides requires vesicular fusion and the formation of a palisade-shaped membrane-building structure.
- Yue Chen
- , Jia Liu
- & Xingzhong Liu
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Fungal secondary metabolism is governed by an RNA-binding protein CsdA/RsdA complex
RsdA regulates the secondary metabolism in fungi. Here the authors show that RNA-binding protein CsdA interacts with RsdA protein and regulates expression of RsdA, coordinating secondary metabolism in fungi.
- Zili Song
- , Shuang Zhou
- & Wen-Bing Yin
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Microglia are not protective against cryptococcal meningitis
Cryptococcal meningitis is a life-threatening fungal infection. Here, Mohamed et al find that brain resident microglia do not provide protection against this infection and instead are a site where the fungus may access the micronutrient copper.
- Sally H. Mohamed
- , Man Shun Fu
- & Rebecca A. Drummond
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Structural adaptation of fungal cell wall in hypersaline environment
Solid-state NMR snapshots of Aspergillus sydowii and other halophilic fungal species reveal the structural rearrangement of polysaccharides and proteins, which create a thick, stiff and hydrophobic cell wall to withstand external stress and thrive in hypersaline environment
- Liyanage D. Fernando
- , Yordanis Pérez-Llano
- & Tuo Wang
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Fungal antigenic variation using mosaicism and reassortment of subtelomeric genes’ repertoires
Here the authors find that surface antigenic variation of the human pathogenic fungus Pneumocystis jirovecii involves mosaicism and reassortment of the repertoire of 80 genes present in each strain, from which single genes are retrieved for mutually exclusive expression.
- Caroline S. Meier
- , Marco Pagni
- & Philippe M. Hauser
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Regulation of symbiotic interactions and primitive lichen differentiation by UMP1 MAP kinase in Umbilicaria muhlenbergii
The mechanisms regulating fungal-algal interactions during the formation of lichen symbioses are not clear. Here, Wang et al. establish conditions conducive to symbiotic interactions and lichen differentiation using a fungus amenable to genetic manipulation, showing the importance of a MAP kinase in lichen development.
- Yanyan Wang
- , Rong Li
- & Jin-Rong Xu
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Origin of fungal hybrids with pathogenic potential from warm seawater environments
Most clinical isolates of the pathogenic yeast Candida orthopsilosis are hybrids of two parental lineages, only one of which has been identified. Here, del Olmo et al. show that C. orthopsilosis strains isolated from warm seawater are hybrids closely related to clinical isolates, and identify the missing parental lineage, thus providing a more complete view of the genomic evolution of this species.
- Valentina del Olmo
- , Verónica Mixão
- & Toni Gabaldón
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Invasive Californian death caps develop mushrooms unisexually and bisexually
The death cap mushroom Amanita phalloides is invading California but little is known about how it spreads through forests. Wang et al. discover that this fungus can develop mushrooms and sporulate without mating; the nuclei involved in unisexuality appear to have persisted in invaded habitats for decades.
- Yen-Wen Wang
- , Megan C. McKeon
- & Anne Pringle
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C-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity
Receptor dimerization can modulate immune responses during various microbial infections. Here, the authors show that C-type lectin receptor-2d (CLEC2D) negatively regulates antifungal immunity through forming homodimers or heterodimers with TLR2.
- Fan Li
- , Hui Wang
- & Xin-Ming Jia
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Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry
Here, Ristow et al show that the environmental fungus Cryptococcus adapts to the higher carbon dioxide levels present in human tissue through activation of the Target-of-Rapamycin stress response pathway leading to reorganization of its outer membrane lipids and host adaptation.
- Laura C. Ristow
- , Andrew J. Jezewski
- & Damian J. Krysan
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Global diversity and biogeography of potential phytopathogenic fungi in a changing world
Phytopathogenic fungi threaten global food security but their global diversity and biogeography are underexplored. Using more than 20,000 globally distributed samples, this study builds a global atlas of phytopathogenic fungi, and predicts that that their diversity and invasion potential will increase globally by the end of this century, especially in forest and cropland ecosystems.
- Pengfa Li
- , Leho Tedersoo
- & Jiandong Jiang
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Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures
Candida glabrata bloodstream infections are thought to be mostly caused by a single strain. Here, the authors describe genotypic and phenotypic diversity of Candida glabrata in ten individual blood cultures, and find diversity in drug susceptibility and virulence within patients.
- Hassan Badrane
- , Shaoji Cheng
- & M. Hong Nguyen
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Ustilago maydis PR-1-like protein has evolved two distinct domains for dual virulence activities
Plant PR-1 proteins participate in defense responses against pathogens. Here, the authors show that PR-1-like proteins from the plant pathogenic fungus Ustilago maydis are important for virulence by detecting plant-derived phenolics and modulating plant PR-1-mediated defenses.
- Yu-Han Lin
- , Meng-Yun Xu
- & Lay-Sun Ma
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Plant immunity suppression by an exo-β-1,3-glucanase and an elongation factor 1α of the rice blast fungus
Fungal cell walls release β-1,3-glucan fragments that trigger plant immunity. Here, the authors show that a glucanase (Ebg1) of the blast fungus Magnaporthe oryzae suppresses plant immunity by hydrolyzing β-1,3-glucan. At the same time, Ebg1 induces plant immune responses that are dampened by a fungal protein that interacts with Ebg1.
- Hang Liu
- , Xunli Lu
- & You-Liang Peng
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Surface frustration re-patterning underlies the structural landscape and evolvability of fungal orphan candidate effectors
Pathogens secrete effectors that evade host immunity and promote disease. The authors identify effectors conserved across fungi in which low structure divergence associates with surface energetics variation, conferring robustness and evolvability.
- Mark C. Derbyshire
- & Sylvain Raffaele
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Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen
Fungal pathogens are recognised and phagocytosed by macrophages in the early stages of infection. Here, Onyishi et al. identify a crosstalk between Toll Like Receptor 4 and Macrophage Scavenger Receptor 1 in the regulation of Cryptococcus neoformans uptake.
- Chinaemerem U. Onyishi
- , Guillaume E. Desanti
- & Robin C. May
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| Open Access
Structure, catalysis, chitin transport, and selective inhibition of chitin synthase
Chitin, the second most abundant natural polysaccharide in nature, is synthesized by chitin synthases, which are recognized as targets for antifungal and anti-insect drugs. Here the authors determine cryo-EM structures of the chitin synthase, which reveal its activation, catalytic and inhibitory mechanisms
- Dan-Dan Chen
- , Zhao-Bin Wang
- & Lin Bai
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Multifactor transcriptional control of alternative oxidase induction integrates diverse environmental inputs to enable fungal virulence
Metabolic flexibility allows fungi to invade hostile niches. Here, Liu et al. dissect the molecular mechanisms by which Candida albicans upregulates virulence-enabling alternative oxidase expression in response to host-relevant respiratory stresses.
- Zhongle Liu
- , Pauline Basso
- & Leah E. Cowen
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Fungal small RNAs ride in extracellular vesicles to enter plant cells through clathrin-mediated endocytosis
Fungal pathogen Botrytis cinerea can send sRNAs to plant cells to suppress plant immunity. Here the authors demonstrate that B. cinerea utilizes extracellular vesicles (EVs) to secrete Bc-sRNAs, which are then internalized by plant cells through clathrin-mediated endocytosis (CME).
- Baoye He
- , Huan Wang
- & Hailing Jin
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Genome-scale metabolic modeling of Aspergillus fumigatus strains reveals growth dependencies on the lung microbiome
Here, the authors generate strain-specific genome-scale metabolic models of Aspergillus fumigatus and analyze fungal metabolism of infection of the lung of cystic fibrosis patients, finding that the fungus shapes the lung microbiome to promote its own growth.
- Mohammad H. Mirhakkak
- , Xiuqiang Chen
- & Gianni Panagiotou
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A protein kinase coordinates cycles of autophagy and glutaminolysis in invasive hyphae of the fungus Magnaporthe oryzae within rice cells
The blast fungus Magnaporthe oryzae produces invasive hyphae in living rice cells during early infection. Here, the authors show that a fungal protein kinase promotes this biotrophic growth phase by coordinating cycles of autophagy and glutaminolysis in invasive hyphae.
- Gang Li
- , Ziwen Gong
- & Richard A. Wilson
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T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS
Cryptococcus-associated immune reconstitution inflammatory syndrome is a condition found in immunocompromised patients on antiretroviral therapy and characterized by numerous symptoms, including pulmonary distress. Here, Kawano et al use a mouse model to characterize the processes underlying this pulmonary dysfunction.
- Tasuku Kawano
- , Jinyan Zhou
- & Makoto Inoue
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Patterns and determinants of the global herbivorous mycobiome
Anaerobic gut fungi are a functionally important component of mammalian herbivores’ microbiomes. Here, the authors surveys anaerobic gut fungi in 34 species of ruminants and hindgut fermenters, assessing their patterns and identifying 56 novel genera.
- Casey H. Meili
- , Adrienne L. Jones
- & Mostafa S. Elshahed
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| Open Access
Candida albicans exploits N-acetylglucosamine as a gut signal to establish the balance between commensalism and pathogenesis
The mechanisms by which opportunistic pathogens shift between commensalism and pathogenesis remains poorly understood. Here, the authors show that N-acetylglucosamine, a carbon source enriched in the gut, plays a role in modulating commensal-pathogenic balance in Candida albicans.
- Dandan Yang
- , Mao Zhang
- & Yang Lu
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A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi
Hsp110 chaperones play important roles in protein homeostasis in eukaryotes. Here, the authors identify a small compound that inhibits fungal Hsp110s as well as the growth and viability of the pathogenic fungus Candida albicans, supporting Hsp110s as targets for development of new antifungal drugs.
- Liqing Hu
- , Cancan Sun
- & Qinglian Liu
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| Open Access
Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions
Here, Seelbinder et al. show high Candida levels in cancer patients’ stool to correlate with greater metabolically flexibility but less robust bacterial communities and, combined with machine learning models to predict Candida levels from bacterial data, suggest that lactate producing bacteria may fuel Candida overgrowth in the gut during dysbiosis.
- Bastian Seelbinder
- , Zoltan Lohinai
- & Gianni Panagiotou
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Inositol pyrophosphates activate the vacuolar transport chaperone complex in yeast by disrupting a homotypic SPX domain interaction
Pipercevic et al resolve how inositol molecules activate the VTC protein complex. The VTC complex stores phosphate in yeast and is controlled by SPX domains. The inositol molecules break an interaction between SPX domains to activate the complex.
- Joka Pipercevic
- , Bastian Kohl
- & Sebastian Hiller
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Hybrids of RNA viruses and viroid-like elements replicate in fungi
RNA viruses are defined by linear RNA genomes encoding an RNA-dependent RNA polymerase, while viroid-like elements consist of small, single-stranded, circular RNA genomes that, in some cases, encode self-cleaving catalytic RNAs. Here, the authors identify over 20,000 candidate viroid-like elements, and show that infectious agents of fungi display hybrid features of viroid-like RNAs and RNA viruses.
- Marco Forgia
- , Beatriz Navarro
- & Marcos de la Peña
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| Open Access
Glucose depletion enables Candida albicans mating independently of the epigenetic white-opaque switch
The pathogenic fungus Candida albicans can switch between a mating-competent form (“opaque” cells) and a form that is thought to be essentially sterile (“white” cells). Here, the authors show that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating.
- Guobo Guan
- , Li Tao
- & Guanghua Huang
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| Open Access
Major proliferation of transposable elements shaped the genome of the soybean rust pathogen Phakopsora pachyrhizi
Asian soybean rust caused by Phakopsora pachyrhizi is an important plant pathogen, but an accurate genome assembly for this fungus has been lacking. This study sequenced three independent P. pachyrhizi isolates and generated reference quality assemblies and genome annotations, representing a critical step for further in-depth studies of this pathogen and the development of new methods of control.
- Yogesh K. Gupta
- , Francismar C. Marcelino-Guimarães
- & H. Peter van Esse
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Chance promoter activities illuminate the origins of eukaryotic intergenic transcriptions
It is debated whether the pervasive intergenic transcription from eukaryotic genomes has functional significance. Here, Xu et al. find that only 1–5% of yeast intergenic transcription is unattributable to chance promoter activity or neighboring gene expression.
- Haiqing Xu
- , Chuan Li
- & Jianzhi Zhang
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Large-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
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Macrophage 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
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Reciprocal 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
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| Open Access
Regulatory 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
The vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans