Global Control of Dimorphism and Virulence in Fungi

Nemecek, Julie; Wüthrich, Marcel; Klein, Bruce S.

doi:10.1126/science.1124105

Cited by 332 publications

(347 citation statements)

References 28 publications

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“…Therefore, morphological and physiological plasticity allows fungi to rapidly adapt to changing extracellular conditions. Species-specific signaling and morphological features appear to be a direct result of fungal attempts to survive as new microenvironments, and their particular cell stresses, were encountered (Hogan and Klein 1994;Newman et al 1995;Batanghari et al 1998;Sebghati et al 2000;Gow et al 2002;Brandhorst et al 2004;Rappleye et al 2004Rappleye et al , 2007Gantner et al 2005;Nemecek et al 2006;Gauthier and Klein 2008;Nather and Munro 2008;Mora-Montes et al 2011;. The concerted action of morphotype and physiological changes in the context of a particular environment are therefore critical for successful fungal adaptation (Butler et al 2009;O'Connor et al 2010).…”

Section: Resultsmentioning

confidence: 99%

Fungal Morphogenesis

Lin

Alspaugh

Liu

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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Morphogenesis in fungi is often induced by extracellular factors and executed by fungal genetic factors. Cell surface changes and alterations of the microenvironment often accompany morphogenetic changes in fungi. In this review, we will first discuss the general traits of yeast and hyphal morphotypes and how morphogenesis affects development and adaptation by fungi to their native niches, including host niches. Then we will focus on the molecular machinery responsible for the two most fundamental growth forms, yeast and hyphae. Last, we will describe how fungi incorporate exogenous environmental and host signals together with genetic factors to determine their morphotype and how morphogenesis, in turn, shapes the fungal microenvironment. PROPERTIES OF MORPHOGENESIS IN FUNGAL CELLS

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Section: Resultsmentioning

confidence: 99%

Fungal Morphogenesis

Lin

Alspaugh

Liu

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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“…The only other factor identified to date that is necessary for yeast-phase growth in H. capsulatum is DRK1 (28). Although the morphologic phenotype of the ryp1 and drk1 mutants is very similar at 37°C, they have opposing phenotypes at room temperature: The ryp1 mutant appears to conidiate inappropriately under aerated growth conditions (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…Regulation of morphology, gene expression, and virulence in response to temperature is exhibited by the entire group of systemic dimorphic fungi (10) (which includes H. capsulatum, Blastomyces dermatitidis, Coccidioides spp., Paracoccidioides brasiliensis, Penicillium marneffei, and Sporothrix schenkii, all of which are pathogens of humans). Recent work identified a conserved histidine kinase, DRK1 (dimorphism regulating kinase), which is required for yeast-phase growth at 37°C in both B. dermatitidis and H. capsulatum (28), suggesting that some elements of cell-shape regulation are conserved in these fungi. It remains to be determined whether orthologs of RYP1 in the other systemic dimorphic fungi might regulate morphology at host temperature.…”

Section: Discussionmentioning

confidence: 99%

Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator

Nguyen

Sil

2008

Proc. Natl. Acad. Sci. U.S.A.

174

207

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Histoplasma capsulatum, a fungal pathogen of humans, switches from a filamentous spore-forming mold in the soil to a pathogenic budding-yeast form in the human host. This morphologic switch, which is exhibited by H. capsulatum and a group of evolutionarily related fungal pathogens, is regulated by temperature. Using insertional mutagenesis, we identified a gene, RYP1 (required for yeast phase growth), which is required for yeast-form growth at 37°C. ryp1 mutants are constitutively filamentous irrespective of temperature. Ryp1 is a member of a family of fungal proteins that includes Wor1, a master transcriptional regulator of the whiteopaque transition required for mating in Candida albicans. Ryp1 associates with its own upstream regulatory region, consistent with a direct role in transcriptional control, and both the protein and its transcript accumulate to high levels in wild-type yeastphase cells. Microarray analysis demonstrated that Ryp1 is required for the expression of the vast majority of yeast-specific genes, including two genes linked to virulence. Thus, Ryp1 appears to be a critical transcriptional regulator of a temperature-regulated morphologic switch in H. capsulatum.fungal pathogenesis ͉ gene regulation ͉ morphology

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“…With the exception of Cryptococcus, each of these species is ''dimorphic,'' growing as a saprophytic mold form at ambient temperatures (i.e., the soil environment) and a parasitic yeast (or spherule) form at mammalian body temperatures. Mold-produced conidia (or spores) that are inhaled into the lung germinate into yeast, and this conversion is absolutely required for pathogenicity (3,4), suggesting that yeast phase-specific characteristics include determinants important for virulence.…”

mentioning

confidence: 99%

Histoplasma capsulatumα-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor

Rappleye

Eissenberg

Goldman

2007

Proc. Natl. Acad. Sci. U.S.A.

378

339

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Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as ␤-glucans. A less common polysaccharide, ␣-(1,3)-glucan, is a cell wall constituent of most fungal respiratory pathogens and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism by which ␣-(1,3)-glucan promotes fungal virulence is unknown. Here, we show that ␣-(1,3)-glucan is present in the outermost layer of the Histoplasma capsulatum yeast cell wall and contributes to pathogenesis by concealing immunostimulatory ␤-glucans from detection by host phagocytic cells. Production of proinflammatory TNF␣ by phagocytes was suppressed either by the presence of the ␣-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host ␤-glucan receptor dectin-1. Thus, we have functionally defined key molecular components influencing the initial host-pathogen interaction in histoplasmosis and have revealed an important mechanism by which H. capsulatum thwarts the host immune system. Furthermore, we propose that the degree of this evasion contributes to the difference in pathogenic potential between dimorphic fungal pathogens and opportunistic fungi.cell wall ͉ fungal pathogenesis ͉ virulence factor ͉ dectin-1 ͉ macrophage

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Global Control of Dimorphism and Virulence in Fungi

Cited by 332 publications

References 28 publications

Fungal Morphogenesis

Fungal Morphogenesis

Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator

Histoplasma capsulatumα-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor

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