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PLoS Pathogens Jan 2023Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse...
Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse virulence functions including surface adhesins that ensure biofilm integrity. Biofilm formation, virulence, and hypha-associated gene expression all depend upon the transcription factor Efg1. This transcription factor has been characterized extensively in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored in other clinical isolates. Here we define a principal set of Efg1-responsive genes whose expression is significantly altered by an efg1Δ/Δ mutation across 17 clinical isolates. This principal gene set includes 68 direct Efg1 targets, whose 5' regions are bound by Efg1 in five clinical isolates, and 42 indirect Efg1 targets, whose 5' regions are not detectably bound by Efg1. Three direct Efg1 target genes encode transcription factors-BRG1, UME6, and WOR3 -whose increased expression in an efg1Δ/Δ mutant restores expression of multiple indirect and direct principal targets, as well as biofilm formation ability. Although BRG1 and UME6 are well known positive regulators of hypha-associated genes and biofilm formation, WOR3 is best known as an antagonist of Efg1 in the sexual mating pathway. We confirm the positive role of WOR3 in biofilm formation with the finding that a wor3Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo biofilm model. Positive control of Efg1 direct target genes by other Efg1 direct target genes-BRG1, UME6, and WOR3 -may buffer principal Efg1-responsive gene expression against the impact of genetic variation in the C. albicans species.
Topics: Candida albicans; Fungal Proteins; Gene Expression Regulation, Fungal; Transcription Factors; Biofilms; Mutation; Hyphae
PubMed: 36696432
DOI: 10.1371/journal.ppat.1011109 -
Nature Communications Jan 2022Filamentous actinobacteria such as Streptomyces undergo two distinct modes of cell division, leading to partitioning of growing hyphae into multicellular compartments...
Filamentous actinobacteria such as Streptomyces undergo two distinct modes of cell division, leading to partitioning of growing hyphae into multicellular compartments via cross-walls, and to septation and release of unicellular spores. Specific determinants for cross-wall formation and the importance of hyphal compartmentalization for Streptomyces development are largely unknown. Here we show that SepX, an actinobacterial-specific protein, is crucial for both cell division modes in Streptomyces venezuelae. Importantly, we find that sepX-deficient mutants grow without cross-walls and that this substantially impairs the fitness of colonies and the coordinated progression through the developmental life cycle. Protein interaction studies and live-cell imaging suggest that SepX contributes to the stabilization of the divisome, a mechanism that also requires the dynamin-like protein DynB. Thus, our work identifies an important determinant for cell division in Streptomyces that is required for cellular development and sporulation.
Topics: Bacterial Proteins; Biological Phenomena; Cell Division; Cell Wall; Hyphae; Life Cycle Stages; Spores, Bacterial; Streptomyces
PubMed: 35013186
DOI: 10.1038/s41467-021-27638-1 -
Virulence 2015Candida albicans is both a commensal microorganism in healthy individuals and a major fungal pathogen causing high mortality in immunocompromised patients. Yeast-hypha... (Review)
Review
Candida albicans is both a commensal microorganism in healthy individuals and a major fungal pathogen causing high mortality in immunocompromised patients. Yeast-hypha morphological transition is a well known virulence trait of C. albicans. Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs). In this review, we summarize the PRRs involved in the recognition of C. albicans in epithelial cells, endothelial cells, and phagocytic cells separately. We figure out the differential recognition of yeasts and hyphae, the findings on PRR-deficient mice, and the discoveries on human PRR-related single nucleotide polymorphisms (SNPs).
Topics: Animals; Candida albicans; Dendritic Cells; Endothelial Cells; Epithelial Cells; Host-Pathogen Interactions; Humans; Hyphae; Immunity, Innate; Mice; Phagocytes; Polymorphism, Single Nucleotide; Receptors, Pattern Recognition
PubMed: 25714264
DOI: 10.1080/21505594.2015.1014270 -
Protein & Cell May 2012Predacious fungi form specialized hyphae structures to trap nematodes and other microscopic animals. Among the six kinds of trapping devices, the constricting ring is... (Review)
Review
Predacious fungi form specialized hyphae structures to trap nematodes and other microscopic animals. Among the six kinds of trapping devices, the constricting ring is the only one that actively captures nematodes. When a nematode enters the aperture of the ring, which is formed by three cells, the cells rapidly triple their volume, close the aperture and hold the nematode in place. Hyphae then penetrate and consume the nematode. This paper reviews the data and hypotheses on conserving the evolution of constricting rings and their cytological and molecular mechanisms.
Topics: Adaptation, Physiological; Animals; Fungi; Hyphae; Morphogenesis; Nematoda
PubMed: 22528749
DOI: 10.1007/s13238-012-2031-8 -
MSphere Dec 2018The yeast undergoes a morphological transition from yeast-to-hyphal growth in response to environmental conditions. A forward genetic screen was used to identify...
The yeast undergoes a morphological transition from yeast-to-hyphal growth in response to environmental conditions. A forward genetic screen was used to identify mutants that reliably remain in the yeast phase, which were then assessed by whole-genome sequencing. All the mutants identified, so named because of their colony morphology, exhibit independent loss of DNA at a repetitive locus made up of interspersed ribosomal DNA and short 10- to 40-mer telomere-like repeats. The loss of repetitive DNA is associated with downregulation of genes with stress response elements (5'-CCCCT-3') and upregulation of genes with cell cycle box (5'-ACGCG-3') motifs in their promoter region. The stress response element is bound by the transcription factor Msn2p in We confirmed that the (Yl) ortholog is required for hyphal growth and found that overexpression of Yl enables hyphal growth in strains. The cell cycle box is bound by the Mbp1p/Swi6p complex in to regulate G-to-S phase progression. We found that overexpression of either the Yl or Yl homologs decreased hyphal growth and that deletion of either Yl or Yl promotes hyphal growth in strains. A second forward genetic screen for reversion to hyphal growth was performed with the mutant to identify additional genetic factors regulating hyphal growth in Thirteen of the mutants sequenced from this screen had coding mutations in five kinases, including the histidine kinases Yl and Yl and kinases of the high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP) kinase cascade Yl, Yl, and Yl Together, these results demonstrate that transitions to hyphal growth in response to stress through multiple signaling pathways. Many yeasts undergo a morphological transition from yeast-to-hyphal growth in response to environmental conditions. We used forward and reverse genetic techniques to identify genes regulating this transition in We confirmed that the transcription factor Yl is required for the transition to hyphal growth and found that signaling by the histidine kinases Yl and Yl as well as the MAP kinases of the HOG pathway (Yl, Yl, and Yl) regulates the transition to hyphal growth. These results suggest that transitions to hyphal growth in response to stress through multiple kinase pathways. Intriguingly, we found that a repetitive portion of the genome containing telomere-like and rDNA repeats may be involved in the transition to hyphal growth, suggesting a link between this region and the general stress response.
Topics: DNA Mutational Analysis; Fungal Proteins; Gene Expression Regulation, Fungal; Genetic Testing; Hyphae; Whole Genome Sequencing; Yarrowia
PubMed: 30518677
DOI: 10.1128/mSphere.00541-18 -
Journal of Clinical Microbiology Apr 2018
Topics: Child; Dacryocystitis; Drainage; Eye; Female; Humans; Hyphae; Mucorales; Mucormycosis; Orbital Diseases; Tomography, X-Ray Computed
PubMed: 29581315
DOI: 10.1128/JCM.00463-16 -
PLoS Genetics Jan 2022Ssn3, also known as Cdk8, is a member of the four protein Cdk8 submodule within the multi-subunit Mediator complex involved in the co-regulation of transcription. In...
Ssn3, also known as Cdk8, is a member of the four protein Cdk8 submodule within the multi-subunit Mediator complex involved in the co-regulation of transcription. In Candida albicans, the loss of Ssn3 kinase activity affects multiple phenotypes including cellular morphology, metabolism, nutrient acquisition, immune cell interactions, and drug resistance. In these studies, we generated a strain in which Ssn3 was replaced with a functional variant of Ssn3 that can be rapidly and selectively inhibited by the ATP analog 3-MB-PP1. Consistent with ssn3 null mutant and kinase dead phenotypes, inhibition of Ssn3 kinase activity promoted hypha formation. Furthermore, the increased expression of hypha-specific genes was the strongest transcriptional signal upon inhibition of Ssn3 in transcriptomics analyses. Rapid inactivation of Ssn3 was used for phosphoproteomic studies performed to identify Ssn3 kinase substrates associated with filamentation potential. Both previously validated and novel Ssn3 targets were identified. Protein phosphorylation sites that were reduced specifically upon Ssn3 inhibition included two sites in Flo8 which is a transcription factor known to positively regulate C. albicans morphology. Mutation of the two Flo8 phosphosites (threonine 589 and serine 620) was sufficient to increase Flo8-HA levels and Flo8 dependent transcriptional and morphological changes, suggesting that Ssn3 kinase activity negatively regulates Flo8.Under embedded conditions, when ssn3Δ/Δ and efg1Δ/Δ mutants were hyperfilamentous, FLO8 was essential for hypha formation. Previous work has also shown that loss of Ssn3 activity leads to increased alkalinization of medium with amino acids. Here, we show that the ssn3Δ/Δ medium alkalinization phenotype, which is dependent on STP2, a transcription factor involved in amino acid utilization, also requires FLO8 and EFG1. Together, these data show that Ssn3 activity can modulate Flo8 and its direct and indirect interactions in different ways, and underscores the potential importance of considering Ssn3 function in the control of transcription factor activities.
Topics: Candida albicans; Cyclin-Dependent Kinase 8; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Hyphae; Loss of Function Mutation; Phosphorylation; Proteomics; Purines; Transcription Factors
PubMed: 34982775
DOI: 10.1371/journal.pgen.1009622 -
Scientific Reports Jul 2017Hyphae of higher fungi grow at their tips and are compartmentalized by porous septa that enable inter-compartmental cytoplasmic streaming. Woronin bodies discontinue...
Hyphae of higher fungi grow at their tips and are compartmentalized by porous septa that enable inter-compartmental cytoplasmic streaming. Woronin bodies discontinue cytoplasmic streaming by plugging the septal pores. Here, it was assessed whether apical compartments of Aspergillus niger sustain their own growth or whether their growth depends on subapical compartments. Hyphae of wildtype and the ΔhexA strain, lacking Woronin bodies, had a similar morphology and growth rate. A total of 58% and 17% of the hyphae continued growing, respectively, after dissecting the 2 compartment. Extension rate of the apical compartments that continued growing was not affected, even when the carbon or nitrogen source was limiting. Thus, apical compartments are self-sustaining in growth. It was also shown that the first 8 subapical compartments of the wildtype, but not of the ΔhexA strain, function as a backup system for growth by forming new branches when their apical neighbouring compartment has been damaged. This backup system is pivotal in nature because of the life style of fungi to continuously explore their surrounding substrate that may prove hostile.
Topics: Aspergillus niger; Fungal Proteins; Genetic Association Studies; Hyphae; Sequence Deletion
PubMed: 28729612
DOI: 10.1038/s41598-017-06422-6 -
Journal of Microbiology (Seoul, Korea) Mar 2016Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions... (Review)
Review
Candida albicans is a human fungal pathogen capable of causing lethal systemic infections. The plasma membrane plays key roles in virulence because it not only functions as a protective barrier, it also mediates dynamic functions including secretion of virulence factors, cell wall synthesis, invasive hyphal morphogenesis, endocytosis, and nutrient uptake. Consistent with this functional complexity, the plasma membrane is composed of a wide array of lipids and proteins. These components are organized into distinct domains that will be the topic of this review. Some of the plasma membrane domains that will be described are known to act as scaffolds or barriers to diffusion, such as MCC/eisosomes, septins, and sites of contact with the endoplasmic reticulum. Other zones mediate dynamic processes, including secretion, endocytosis, and a special region at hyphal tips that facilitates rapid growth. The highly organized architecture of the plasma membrane facilitates the coordination of diverse functions and promotes the pathogenesis of C. albicans.
Topics: Candida albicans; Candidiasis; Cell Membrane; Endocytosis; Fungal Proteins; Humans; Hyphae; Models, Molecular; Virulence; Virulence Factors
PubMed: 26920878
DOI: 10.1007/s12275-016-5621-y -
PloS One 2014Cryptococcus gattii is a basidiomycetous human fungal pathogen that typically causes infection in tropical and subtropical regions and is responsible for an ongoing...
Cryptococcus gattii is a basidiomycetous human fungal pathogen that typically causes infection in tropical and subtropical regions and is responsible for an ongoing outbreak in immunocompetent individuals on Vancouver Island and in the Pacific Northwest of the US. Pathogenesis of this species may be linked to its sexual cycle that generates infectious propagules called basidiospores. A marked predominance of only one mating type (α) in clinical and environmental isolates suggests that a-α opposite-sex reproduction may be infrequent or geographically restricted, raising the possibility of an alternative unisexual cycle involving cells of only α mating type, as discovered previously in the related pathogenic species Cryptococcus neoformans. Here we report observation of hallmark features of unisexual reproduction in a clinical isolate of C. gattii (isolate 97/433) and describe genetic and environmental factors conducive to this sexual cycle. Our results are consistent with population genetic evidence of recombination in the largely unisexual populations of C. gattii and provide a useful genetic model for understanding how novel modes of sexual reproduction may contribute to evolution and virulence in this species.
Topics: Cryptococcus gattii; Fruiting Bodies, Fungal; Genes, Mating Type, Fungal; Genome, Fungal; Hyphae; MAP Kinase Signaling System; Ploidies
PubMed: 25337713
DOI: 10.1371/journal.pone.0111089