scholarly journals Asexual Propagation of a Virulent Clone Complex in a Human and Feline Outbreak of Sporotrichosis

2014 ◽  
Vol 14 (2) ◽  
pp. 158-169 ◽  
Author(s):  
Marcus de Melo Teixeira ◽  
Anderson Messias Rodrigues ◽  
Clement K. M. Tsui ◽  
Luiz Gonzaga Paulo de Almeida ◽  
Anne D. Van Diepeningen ◽  
...  
Keyword(s):  
Genetic Variability ◽  
Mating Type ◽  
Sequence Data ◽  
Fungal Infections ◽  
Haplotype Diversity ◽  
Sporothrix Schenckii ◽  
Mitogen Activated Protein Kinase ◽  
Comparative Genomic ◽  
Asexual Propagation ◽  
Content Type

ABSTRACT Sporotrichosis is one of the most frequent subcutaneous fungal infections in humans and animals caused by members of the plant-associated, dimorphic genus Sporothrix . Three of the four medically important Sporothrix species found in Brazil have been considered asexual as no sexual stage has ever been reported in Sporothrix schenckii , Sporothrix brasiliensis , or Sporothrix globosa . We have identified the mating type ( MAT ) loci in the S. schenckii (strain 1099-18/ATCC MYA-4821) and S. brasiliensis (strain 5110/ATCC MYA-4823) genomes by using comparative genomic approaches to determine the mating type ratio in these pathogen populations. Our analysis revealed the presence of a MAT1-1 locus in S. schenckii while a MAT1-2 locus was found in S. brasiliensis representing genomic synteny to other Sordariomycetes . Furthermore, the components of the mitogen-activated protein kinase (MAPK)-pheromone pathway, pheromone processing enzymes, and meiotic regulators have also been identified in the two pathogens, suggesting the potential for sexual reproduction. The ratio of MAT1-1 to MAT1-2 was not significantly different from 1:1 for all three Sporothrix species, but the population of S. brasiliensis in the outbreaks originated from a single mating type. We also explored the population genetic structure of these pathogens using sequence data of two loci to improve our knowledge of the pattern of geographic distribution, genetic variation, and virulence phenotypes. Population genetics data showed significant population differentiation and clonality with a low level of haplotype diversity in S. brasiliensis isolates from different regions of sporotrichosis outbreaks in Brazil. In contrast, S. schenckii isolates demonstrated a high degree of genetic variability without significant geographic differentiation, indicating the presence of recombination. This study demonstrated that two species causing the same disease have contrasting reproductive strategies and genetic variability patterns.

scholarly journals The Unfolded Protein Response Regulates Pathogenic Development of Ustilago maydis by Rok1-Dependent Inhibition of Mating-Type Signaling

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Lara Schmitz ◽  
Melina Ayaka Schwier ◽  
Kai Heimel
Keyword(s):  
Unfolded Protein Response ◽  
Mating Type ◽  
Ustilago Maydis ◽  
Mitogen Activated Protein Kinase ◽  
In Planta ◽  
Fungal Virulence ◽  
Content Type ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

ABSTRACT Fungal pathogens require the unfolded protein response (UPR) to maintain protein homeostasis of the endoplasmic reticulum (ER) during pathogenic development. In the corn smut fungus Ustilago maydis, pathogenic development is controlled by the a and b mating-type loci. The UPR is specifically activated after plant penetration and required for efficient secretion of effectors and suppression of the plant defense response. The interaction between the UPR regulator Cib1 and the central developmental regulator Clp1 modulates the pathogenic program and triggers fungal colonization of the host plant. By contrast, when activated before plant penetration, the UPR interferes with fungal virulence by reducing expression of bE and bW, the central regulators of pathogenic development encoded by the b mating-type locus. Here, we show that this inhibitory effect results from UPR-mediated suppression of the pheromone response pathway upstream of the b regulatory network. UPR activity prompts dephosphorylation of the pheromone-responsive mitogen-activated protein kinase (MAPK) Kpp2, reducing activity of the pheromone response factor Prf1 that regulates expression of bE and bW. Deletion of the dual specificity phosphatase rok1 fully suppressed UPR-dependent inhibition of Kpp2 phosphorylation, formation of infectious filaments, and fungal virulence. Rok1 determines the activity of mating-type signaling pathways and thus the degree of fungal virulence. We propose that UPR-dependent regulation of Rok1 aligns ER physiology with fungal aggressiveness and effector gene expression during biotrophic growth of U. maydis in the host plant. IMPORTANCE The unfolded protein response (UPR) is crucial for endoplasmic reticulum (ER) homeostasis and disease development in fungal pathogens. In the plant-pathogenic fungus Ustilago maydis, the UPR supports fungal proliferation in planta and effector secretion for plant defense suppression. In this study, we uncovered that UPR activity, which is normally restricted to the biotrophic stage in planta, inhibits mating and the formation of infectious filaments by Rok1-dependent dephosphorylation of the pheromone responsive mitogen-activated protein kinase (MAPK) Kpp2. This observation is relevant for understanding how the fungal virulence program is regulated by cellular physiology. UPR-mediated control of mating-type signaling pathways predicts that effector gene expression and the virulence potential are controlled by ER stress levels.

scholarly journals Identification of the Mating-Type (MAT) Locus That Controls Sexual Reproduction of Blastomyces dermatitidis

2012 ◽  
Vol 12 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Wenjun Li ◽  
Thomas D. Sullivan ◽  
Eric Walton ◽  
Anna Floyd Averette ◽  
Sharadha Sakthikumar ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Mating Type ◽  
Genetic Recombination ◽  
Sexual Cycle ◽  
Blastomyces Dermatitidis ◽  
Comparative Genomic ◽  
Dimorphic Fungi ◽  
Content Type ◽  
Long Time ◽  
Northern United States

ABSTRACTBlastomyces dermatitidisis a dimorphic fungal pathogen that primarily causes blastomycosis in the midwestern and northern United States and Canada. While the genes controlling sexual development have been known for a long time, the genes controlling sexual reproduction ofB. dermatitidis(teleomorph,Ajellomyces dermatitidis) are unknown. We identified the mating-type (MAT) locus in theB. dermatitidisgenome by comparative genomic approaches. TheB. dermatitidis MATlocus resembles those of other dimorphic fungi, containing either an alpha-box (MAT1-1) or an HMG domain (MAT1-2) gene linked to theAPN2,SLA2, andCOX13genes. However, in some strains ofB. dermatitidis, theMATlocus harbors transposable elements (TEs) that make it unusually large compared to theMATlocus of other dimorphic fungi. Based on theMATlocus sequences ofB. dermatitidis, we designed specific primers for PCR determination of the mating type. TwoB. dermatitidisisolates of opposite mating types were cocultured on mating medium. Immature sexual structures were observed starting at 3 weeks of coculture, with coiled-hyphae-containing cleistothecia developing over the next 3 to 6 weeks. Genetic recombination was detected in potential progeny by mating-type determination, PCR-restriction fragment length polymorphism (PCR-RFLP), and random amplification of polymorphic DNA (RAPD) analyses, suggesting that a meiotic sexual cycle might have been completed. The F1 progeny were sexually fertile when tested with strains of the opposite mating type. Our studies provide a model for the evolution of theMATlocus in the dimorphic and closely related fungi and open the door to classic genetic analysis and studies on the possible roles of mating and mating type in infection and virulence.

scholarly journals Abolishing Cell Wall Glycosylphosphatidylinositol-Anchored Proteins in Candida albicans Enhances Recognition by Host Dectin-1

2015 ◽  
Vol 83 (7) ◽  
pp. 2694-2704 ◽  
Author(s):  
Hui Shen ◽  
Si Min Chen ◽  
Wei Liu ◽  
Fang Zhu ◽  
Li Juan He ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Host Recognition ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Opportunistic Human Pathogen

Fungi can shield surface pathogen-associated molecular patterns (PAMPs) for evading host immune attack. The most common and opportunistic human pathogen,Candida albicans, can shield β-(1 3)-glucan on the cell wall, one of the major PAMPs, to avoid host phagocyte Dectin-1 recognition. The way to interfere in the shielding process for more effective antifungal defense is not well established. In this study, we found that deletion of theC. albicansGPI7gene, which was responsible for adding ethanolaminephosphate to the second mannose in glycosylphosphatidylinositol (GPI) biosynthesis, could block the attachment of most GPI-anchored cell wall proteins (GPI-CWPs) to the cell wall and subsequently unmask the concealed β-(1,3)-glucan. Neutrophils could kill the uncloakedgpi7mutant more efficiently with an augmented respiratory burst. Thegpi7mutant also stimulated Dectin-1-dependent immune responses of macrophages, including activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways and secretion of specific cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-12p40. Furthermore, thegpi7null mutant could induce an enhanced inflammatory response through promoting significant recruitment of neutrophils and monocytes and could stimulate stronger Th1 and Th17 cell responses to fungal infectionsin vivo. Thesein vivophenotypes also were Dectin-1 dependent. Thus, we assume that GPI-CWPs are involved in the immune mechanism ofC. albicansescaping from host recognition by Dectin-1. Our studies also indicate that the blockage of GPI anchor synthesis is a strategy to inhibitC. albicansevading host recognition.

scholarly journals Basidiomycete Mating Type Genes and Pheromone Signaling

2010 ◽  
Vol 9 (6) ◽  
pp. 847-859 ◽  
Author(s):  
Marjatta Raudaskoski ◽  
Erika Kothe
Keyword(s):  
Sexual Reproduction ◽  
Mating Type ◽  
Schizophyllum Commune ◽  
Small Gtpases ◽  
Mitogen Activated Protein Kinase ◽  
Fruiting Body Formation ◽  
Receptor System ◽  
Content Type ◽  
Discrimination Ability ◽  
Mating Type Genes

ABSTRACT The genome sequences of the basidiomycete Agaricomycetes species Coprinopsis cinerea, Laccaria bicolor, Schizophyllum commune, Phanerochaete chrysosporium, and Postia placenta, as well as of Cryptococcus neoformans and Ustilago maydis, are now publicly available. Out of these fungi, C. cinerea, S. commune, and U. maydis, together with the budding yeast Saccharomyces cerevisiae, have been investigated for years genetically and molecularly for signaling in sexual reproduction. The comparison of the structure and organization of mating type genes in fungal genomes reveals an amazing conservation of genes regulating the sexual reproduction throughout the fungal kingdom. In agaricomycetes, two mating type loci, A, coding for homeodomain type transcription factors, and B, encoding a pheromone/receptor system, regulate the four typical mating interactions of tetrapolar species. Evidence for both A and B mating type genes can also be identified in basidiomycetes with bipolar systems, where only two mating interactions are seen. In some of these fungi, the B locus has lost its self/nonself discrimination ability and thus its specificity while retaining the other regulatory functions in development. In silico analyses now also permit the identification of putative components of the pheromone-dependent signaling pathways. Induction of these signaling cascades leads to development of dikaryotic mycelia, fruiting body formation, and meiotic spore production. In pheromone-dependent signaling, the role of heterotrimeric G proteins, components of a mitogen-activated protein kinase (MAPK) cascade, and cyclic AMP-dependent pathways can now be defined. Additionally, the pheromone-dependent signaling through monomeric, small GTPases potentially involved in creating the polarized cytoskeleton for reciprocal nuclear exchange and migration during mating is predicted.

Pneumocystis Mating-Type Locus and Sexual Cycle during Infection

2021 ◽  
Author(s):  
Philippe M. Hauser
Keyword(s):  
Immune System ◽  
Mating Type ◽  
Host Species ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Sexual Cycle ◽  
Mammalian Host ◽  
Type Locus ◽  
Content Type ◽  
Mating Type Locus

Pneumocystis species colonize mammalian lungs and cause deadly pneumonia if the immune system of the host weakens. Each species presents a specificity for a single mammalian host species. Pneumocystis jirovecii infects humans and provokes pneumonia, which is among the most frequent invasive fungal infections.

scholarly journals Self-Induction ofa/aor α/α Biofilms in Candida albicans Is a Pheromone-Based Paracrine System Requiring Switching

2011 ◽  
Vol 10 (6) ◽  
pp. 753-760 ◽  
Author(s):  
Song Yi ◽  
Nidhi Sahni ◽  
Karla J. Daniels ◽  
Kevin L. Lu ◽  
Guanghua Huang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mating Type ◽  
Biofilm Formation ◽  
Receptor Gene ◽  
Signal Transduction Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Type ◽  
Opposite Mating Type ◽  
Content Type ◽  
Α Pheromone

ABSTRACTLikeMTL-heterozygous (a/α) cells, whiteMTL-homozygous (a/aor α/α) cells ofCandida albicans, to which a minority of opaque cells of opposite mating type have been added, form thick, robust biofilms. The latter biofilms are uniquely stimulated by the pheromone released by opaque cells and are regulated by the mitogen-activated protein kinase signal transduction pathway. However, whiteMTL-homozygous cells, to which opaque cells of opposite mating type have not been added, form thinner biofilms. Mutant analyses reveal that these latter biofilms are self-induced. Self-induction ofa/abiofilms requires expression of the α-receptor geneSTE2and the α-pheromone geneMFα, and self-induction of α/α biofilms requires expression of thea-receptor geneSTE3and thea-pheromone geneMFa. In both cases, deletion ofWOR1, the master switch gene, blocks cells in the white phenotype and biofilm formation, indicating that self-induction depends upon low frequency switching from the white to opaque phenotype. These results suggest a self-induction scenario in which minority opaquea/acells formed by switching secrete, in a mating-type-nonspecific fashion, α-pheromone, which stimulates biofilm formation through activation of the α-pheromone receptor of majority whitea/acells. A similar scenario is suggested for a white α/α cell population, in which minority opaque α/α cells secretea-pheromone. This represents a paracrine system in which one cell type (opaque) signals a second highly related cell type (white) to undergo a complex response, in this case the formation of a unisexual white cell biofilm.

scholarly journals Sequence data from isolated lichen-associated melanized fungi enhance delimitation of two new lineages within Chaetothyriomycetidae

2021 ◽  
Vol 20 (7) ◽  
pp. 911-927
Author(s):  
Lucia Muggia ◽  
Yu Quan ◽  
Cécile Gueidan ◽  
Abdullah M. S. Al-Hatmi ◽  
Martin Grube ◽  
...  
Keyword(s):  
Sequence Data ◽  
Single Species ◽  
Sister Group ◽  
Asexual Propagation ◽  
Dna Sequence Data ◽  
Wide Range ◽  
The Family ◽  
Rock Inhabiting Fungi ◽  
Stable Habitat

AbstractLichen thalli provide a long-lived and stable habitat for colonization by a wide range of microorganisms. Increased interest in these lichen-associated microbial communities has revealed an impressive diversity of fungi, including several novel lineages which still await formal taxonomic recognition. Among these, members of the Eurotiomycetes and Dothideomycetes usually occur asymptomatically in the lichen thalli, even if they share ancestry with fungi that may be parasitic on their host. Mycelia of the isolates are characterized by melanized cell walls and the fungi display exclusively asexual propagation. Their taxonomic placement requires, therefore, the use of DNA sequence data. Here, we consider recently published sequence data from lichen-associated fungi and characterize and formally describe two new, individually monophyletic lineages at family, genus, and species levels. The Pleostigmataceae fam. nov. and Melanina gen. nov. both comprise rock-inhabiting fungi that associate with epilithic, crust-forming lichens in subalpine habitats. The phylogenetic placement and the monophyly of Pleostigmataceae lack statistical support, but the family was resolved as sister to the order Verrucariales. This family comprises the species Pleostigma alpinum sp. nov., P. frigidum sp. nov., P. jungermannicola, and P. lichenophilum sp. nov. The placement of the genus Melanina is supported as a lineage within the Chaetothyriales. To date, this genus comprises the single species M. gunde-cimermaniae sp. nov. and forms a sister group to a large lineage including Herpotrichiellaceae, Chaetothyriaceae, Cyphellophoraceae, and Trichomeriaceae. The new phylogenetic analysis of the subclass Chaetothyiomycetidae provides new insight into genus and family level delimitation and classification of this ecologically diverse group of fungi.

scholarly journals Trends in Antifungal Drug Susceptibility of Cryptococcus neoformans Isolates Obtained through Population-Based Surveillance in South Africa in 2002-2003 and 2007-2008

2011 ◽  
Vol 55 (6) ◽  
pp. 2606-2611 ◽  
Author(s):  
Nelesh P. Govender ◽  
Jaymati Patel ◽  
Marelize van Wyk ◽  
Tom M. Chiller ◽  
Shawn R. Lockhart ◽  
...  
Keyword(s):  
South Africa ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Drug Susceptibility ◽  
Population Based ◽  
Content Type ◽  
Microdilution Method ◽  
Broth Microdilution Method

ABSTRACTCryptococcus neoformansis the most common cause of meningitis among adult South Africans with HIV infection/AIDS. Widespread use of fluconazole for treatment of cryptococcal meningitis and other HIV-associated opportunistic fungal infections in South Africa may lead to the emergence of isolates with reduced fluconazole susceptibility. MIC testing using a reference broth microdilution method was used to determine if isolates with reduced susceptibility to fluconazole or amphotericin B had emerged among cases of incident disease. Incident isolates were tested from two surveillance periods (2002-2003 and 2007-2008) when population-based surveillance was conducted in Gauteng Province, South Africa. These isolates were also tested for susceptibility to flucytosine, itraconazole, voriconazole, and posaconazole. Serially collected isolate pairs from cases at several large South African hospitals were also tested for susceptibility to fluconazole. Of the 487 incident isolates tested, only 3 (0.6%) demonstrated a fluconazole MIC of ≥16 μg/ml; all of these isolates were from 2002-2003. All incident isolates were inhibited by very low concentrations of amphotericin B and exhibited very low MICs to voriconazole and posaconazole. Of 67 cases with serially collected isolate pairs, only 1 case was detected where the isolate collected more than 30 days later had a fluconazole MIC value significantly higher than the MIC of the corresponding incident isolate. Although routine antifungal susceptibility testing of incident isolates is not currently recommended in clinical settings, it is still clearly important for public health to periodically monitor for the emergence of resistance.

scholarly journals An Evolutionary Link between Natural Transformation and CRISPR Adaptive Immunity

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Peter Jorth ◽  
Marvin Whiteley
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Bacterial Diversity ◽  
Natural Transformation ◽  
Bacterial Species ◽  
Comparative Genomic ◽  
Content Type ◽  
Immune Systems ◽  
Adaptive Immune ◽  
Adaptive Immune Systems

ABSTRACTNatural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history ofAggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.IMPORTANCEThe human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogenAggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competentA. actinomycetemcomitansstrains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.

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