scholarly journals The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans

Microbiology ◽  
2009 ◽  
Vol 155 (2) ◽  
pp. 413-423 ◽  
Author(s):  
Rebeca Alonso-Monge ◽  
Sara Carvaihlo ◽  
Cesar Nombela ◽  
Eduardo Rial ◽  
Jesús Pla
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Mapk Pathway ◽  
Pathogenic Fungus ◽  
Atp Synthesis ◽  
Pathogenic Fungi ◽  
Respiratory Metabolism ◽  
Detoxifying Enzymes ◽  
Mitogen Activated Protein ◽  
External Stresses

Signal transduction pathways mediated by mitogen-activated protein kinases (MAPKs) play crucial roles in eukaryotic cells. In the pathogenic fungus Candida albicans the HOG MAPK pathway regulates the response to external stresses (osmotic and oxidative among others) and is involved in morphogenesis and virulence. We show here that the lack of the Hog1 MAPK increases the sensitivity of this fungus to inhibitors of the respiratory chain. hog1 mutants also show an enhanced basal respiratory rate compared to parental strains, and higher levels of intracellular reactive oxygen species despite an increased expression of detoxifying enzymes. We also demonstrate that although oxidative phosphorylation is essentially unaffected, hog1 mutants have an altered mitochondrial membrane potential. Data indicate that hog1-defective mutants are more dependent on mitochondrial ATP synthesis, probably due to an increased cellular ATP demand. Our results therefore link a MAPK pathway with respiratory metabolism in pathogenic fungi.

scholarly journals The Cek1 and Hog1 Mitogen-Activated Protein Kinases Play Complementary Roles in Cell Wall Biogenesis and Chlamydospore Formation in the Fungal Pathogen Candida albicans

2006 ◽  
Vol 5 (2) ◽  
pp. 347-358 ◽  
Author(s):  
B. Eisman ◽  
R. Alonso-Monge ◽  
E. Román ◽  
D. Arana ◽  
C. Nombela ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Map Kinase ◽  
Fungal Pathogen ◽  
Hog Pathway ◽  
Cell Wall Biogenesis ◽  
Chlamydospore Formation ◽  
Mitogen Activated Protein ◽  
Morphological Transitions ◽  
Relationship Of

ABSTRACT The Hog1 mitogen-activated protein (MAP) kinase mediates an adaptive response to both osmotic and oxidative stress in the fungal pathogen Candida albicans. This protein also participates in two distinct morphogenetic processes, namely the yeast-to-hypha transition (as a repressor) and chlamydospore formation (as an inducer). We show here that repression of filamentous growth occurs both under serum limitation and under other partially inducing conditions, such as low temperature, low pH, or nitrogen starvation. To understand the relationship of the HOG pathway to other MAP kinase cascades that also play a role in morphological transitions, we have constructed and characterized a set of double mutants in which we deleted both the HOG1 gene and other signaling elements (the CST20, CLA4, and HST7 kinases, the CPH1 and EFG1 transcription factors, and the CPP1 protein phosphatase). We also show that Hog1 prevents the yeast-to-hypha switch independent of all the elements analyzed and that the inability of the hog1 mutants to form chlamydospores is suppressed when additional elements of the CEK1 pathway (CST20 or HST7) are altered. Finally, we report that Hog1 represses the activation of the Cek1 MAP kinase under basal conditions and that Cek1 activation correlates with resistance to certain cell wall inhibitors (such as Congo red), demonstrating a role for this pathway in cell wall biogenesis.

scholarly journals In Fungal Intracellular Pathogenesis, Form Determines Fate

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Robin C. May ◽  
Arturo Casadevall
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Membrane Integrity ◽  
Pathogenic Fungi ◽  
Morphological Transition ◽  
Physical Damage ◽  
Fungal Cell ◽  
Morphological Transitions ◽  
Pathogenic Microbes ◽  
Phagosomal Membrane

ABSTRACT For pathogenic microbes to survive ingestion by macrophages, they must subvert powerful microbicidal mechanisms within the phagolysosome. After ingestion, Candida albicans undergoes a morphological transition producing hyphae, while the surrounding phagosome exhibits a loss of phagosomal acidity. However, how these two events are related has remained enigmatic. Now Westman et al. (mBio 9:e01226-18, 2018, https://doi.org/10.1128/mBio.01226-18) report that phagosomal neutralization results from disruption of phagosomal membrane integrity by the enlarging hyphae, directly implicating the morphological transition in physical damage that promotes intracellular survival. The C. albicans intracellular strategy shows parallels with another fungal pathogen, Cryptococcus neoformans, where a morphological changed involving capsular enlargement intracellularly is associated with loss of membrane integrity and death of the host cell. These similarities among distantly related pathogenic fungi suggest that morphological transitions that are common in fungi directly affect the outcome of the fungal cell-macrophage interaction. For this class of organisms, form determines fate in the intracellular environment.

scholarly journals IDENTIFIKASI DAN UJI PATOGENISITAS CENDAWAN ENTOMOPATOGEN LOKAL TERHADAP Leptocorisa oratorius

EUGENIA ◽  
2011 ◽  
Vol 17 (3) ◽  
Author(s):  
Emmy Senewe ◽  
Guntur Manengkey
Keyword(s):  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Pathogenic Fungus ◽  
Pathogenic Fungi ◽  
North Sulawesi ◽  
Pathogenicity Tests ◽  
Major Pest ◽  
White Mycelium ◽  
Fusarium Sp ◽  
Leptocorisa Oratorius

ABSTRACT Leptocorisa oratorius is one major pest of rice in North Sulawesi. Hence, it is necessary to control the pest. The research objective was to identify and to test pathogenicity of local  entomopathogen fungi which infected  Leptocorisa oratorius. The pathogens were collected through sampling of L. oratorius which had been infected by the fungi in the field. The pathogenic fungi was isolated using PDA medium, identified followed by inoculation for pathogenecity test.  During several sampling pest, it was found that  L. oratorius was attacked by fungal pathogens in the field. The identification revelead that the fungal pathogens were Beauveria sp and Fusarium sp. Both the fungal pathogen produced white mycelium and could only be distinguished using microscope in the laboratory. Result of pathogenicity tests showed that the two fungal pathogens caused different mortality of the L. oratorius. Mortality of  L. oratorius caused by pathogenic fungus Beauveria sp was  30.3% . Whereas, mortality of  L. oratorius caused by Fusarium sp was only 3.33%. Keywords : pathogenic fungi, entomopathogen, pathogenicity tests, L. oratorius

scholarly journals Two-Component Histidine Phosphotransfer Protein Ypd1 Is Not Essential for Viability in Candida albicans

2014 ◽  
Vol 13 (4) ◽  
pp. 452-460 ◽  
Author(s):  
John Mavrianos ◽  
Chirayu Desai ◽  
Neeraj Chauhan
Keyword(s):  
Candida Albicans ◽  
Fluorescent Protein ◽  
Mapk Pathway ◽  
Response Regulator ◽  
Pathogenic Fungi ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Signaling Mechanism ◽  
Content Type ◽  
Two Component

ABSTRACTProkaryotes and lower eukaryotes, such as yeasts, utilize two-component signal transduction pathways to adapt cells to environmental stress and to regulate the expression of genes associated with virulence. One of the central proteins in this type of signaling mechanism is the phosphohistidine intermediate protein Ypd1. Ypd1 is reported to be essential for viability in the model yeastSaccharomyces cerevisiae. We present data here showing that this is not the case forCandida albicans. Disruption ofYPD1causes cells to flocculate and filament constitutively under conditions that favor growth in yeast form. To determine the function of Ypd1 in the Hog1 mitogen-activated protein kinase (MAPK) pathway, we measured phosphorylation of Hog1 MAPK inypd1Δ/Δ and wild-type strains ofC. albicans. Constitutive phosphorylation of Hog1 was observed in theypd1Δ/Δ strain compared to the wild-type strain. Furthermore, fluorescence microscopy revealed that green fluorescent protein (GFP)-tagged Ypd1 is localized to both the nucleus and the cytoplasm. The subcellular segregation of GFP-tagged Ypd1 hints at an important role(s) of Ypd1 in regulation of Ssk1 (cytosolic) and Skn7 (nuclear) response regulator proteins via phosphorylation inC. albicans. Overall, our findings have profound implications for a mechanistic understanding of two-component signaling pathways inC. albicans, and perhaps in other pathogenic fungi.

scholarly journals The pmk1-like mitogen-activated protein kinase from Lecanicillium (Verticillium) fungicola is not required for virulence on Agaricus bisporus

Microbiology ◽  
2010 ◽  
Vol 156 (5) ◽  
pp. 1439-1447 ◽  
Author(s):  
Patrick D. Collopy ◽  
Richard C. Amey ◽  
Martin J. Sergeant ◽  
Michael P. Challen ◽  
Peter R. Mills ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Agaricus Bisporus ◽  
Plant Pathogens ◽  
Mapk Pathway ◽  
Pathogenic Fungi ◽  
Single Copy ◽  
Mitogen Activated Protein Kinase ◽  
Verticillium Fungicola ◽  
Fungal Plant Pathogens ◽  
Mitogen Activated Protein

In plant-pathogenic fungi, the pmk1 mitogen-activated protein kinase (MAPK) signalling pathway plays an essential role in regulating the development of penetration structures and the sensing of host-derived cues, but its role in other pathosystems such as fungal–fungal interactions is less clear. We report the use of a gene disruption strategy to investigate the pmk1-like MAPK, Lf pmk1 in the development of Lecanicillium fungicola (formerly Verticillium fungicola) infection on the cultivated mushroom Agaricus bisporus. Lf pmk1 was isolated using a degenerate PCR-based approach and was shown to be present in a single copy by Southern blot analysis. Quantitative RT-PCR showed the transcript to be fivefold upregulated in cap lesions compared with pure culture. Agrobacterium-mediated targeted disruption was used to delete a central portion of the Lf pmk1 gene. The resulting mutants showed normal symptom development as assessed by A. bisporus mushroom cap assays, sporulation patterns were normal and there were no apparent changes in overall growth rates. Our results indicate that, unlike the situation in fungal–plant pathogens, the pmk1-like MAPK pathway is not required for virulence in the fungal–fungal interaction between the L. fungicola pathogen and A. bisporus host. This observation may be of wider significance in other fungal–fungal and/or fungal–invertebrate interactions.

scholarly journals Genomic Plasticity of the Human Fungal Pathogen Candida albicans

2010 ◽  
Vol 9 (7) ◽  
pp. 991-1008 ◽  
Author(s):  
Anna Selmecki ◽  
Anja Forche ◽  
Judith Berman
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Drug Exposure ◽  
Pathogenic Fungi ◽  
Lessons Learned ◽  
Common Mechanism ◽  
Content Type ◽  
Genomic Plasticity

ABSTRACTThe genomic plasticity ofCandida albicans, a commensal and common opportunistic fungal pathogen, continues to reveal unexpected surprises. Once thought to be asexual, we now know that the organism can generate genetic diversity through several mechanisms, including mating between cells of the opposite or of the same mating type and by a parasexual reduction in chromosome number that can be accompanied by recombination events (2, 12, 14, 53, 77, 115). In addition, dramatic genome changes can appear quite rapidly in mitotic cells propagatedin vitroas well asin vivo. The detection of aneuploidy in other fungal pathogens isolated directly from patients (145) and from environmental samples (71) suggests that variations in chromosome organization and copy number are a common mechanism used by pathogenic fungi to rapidly generate diversity in response to stressful growth conditions, including, but not limited to, antifungal drug exposure. Since cancer cells often become polyploid and/or aneuploid, some of the lessons learned from studies of genome plasticity inC. albicansmay provide important insights into how these processes occur in higher-eukaryotic cells exposed to stresses such as anticancer drugs.

scholarly journals Role of the Mitogen-Activated Protein Kinase Hog1p in Morphogenesis and Virulence of Candida albicans

1999 ◽  
Vol 181 (10) ◽  
pp. 3058-3068 ◽  
Author(s):  
R. Alonso-Monge ◽  
F. Navarro-García ◽  
G. Molero ◽  
R. Diez-Orejas ◽  
M. Gustin ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Map Kinase ◽  
Pathogenic Fungi ◽  
Mitogen Activated Protein Kinase ◽  
Morphological Alterations ◽  
Mitogen Activated Protein ◽  
Drastic Increase ◽  
Morphological Transitions ◽  
Hyphal Formation

ABSTRACT The relevance of the mitogen-activated protein (MAP) kinase Hog1p in Candida albicans was addressed through the characterization of C. albicans strains without a functional HOG1 gene. Analysis of the phenotype ofhog1 mutants under osmostressing conditions revealed that this mutant displays a set of morphological alterations as the result of a failure to complete the final stages of cytokinesis, with parallel defects in the budding pattern. Even under permissive conditions,hog1 mutants displayed a different susceptibility to some compounds such as nikkomycin Z or Congo red, which interfere with cell wall functionality. In addition, the hog1 mutant displayed a colony morphology different from that of the wild-type strain on some media which promote morphological transitions in C. albicans. We show that C. albicans hog1 mutants are derepressed in the serum-induced hyphal formation and, consistently with this behavior, that HOG1 overexpression inSaccharomyces cerevisiae represses the pseudodimorphic transition. Most interestingly, deletion of HOG1 resulted in a drastic increase in the mean survival time of systemically infected mice, supporting a role for this MAP kinase pathway in virulence of pathogenic fungi. This finding has potential implications in antifungal therapy.

scholarly journals A novel Hsp90 phospho-switch modulates virulence in the major human fungal pathogen Candida albicans

2020 ◽  
Author(s):  
Leenah Alaalm ◽  
Julia L. Crunden ◽  
Mark Butcher ◽  
Ulrike Obst ◽  
Ryann Whealy ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Stress Responses ◽  
Fungal Pathogen ◽  
Drug Targets ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
First Record ◽  
Drug Susceptibility ◽  
Phosphorylation Sites ◽  
Fungal Virulence

The ubiquitous molecular chaperone Hsp90 is a key regulator of cellular proteostasis and environmental stress responses. Hsp90 also regulates cellular morphogenesis, drug resistance, and virulence in human pathogenic fungi, which kill more than 1.6 million patients each year worldwide. Invasive fungal infections are difficult to treat due to the lack of effective antifungal therapies, resulting in mortality rates of up to 95%. As a key regulator of fungal virulence, Hsp90 is an attractive therapeutic target. However, fungal and animal homologs are highly conserved, impeding fungal-specific targeting. Thus, understanding the factors that regulate Hsp90 could provide an alternative strategy aimed at exclusively targeting this regulator of fungal virulence. Here, we demonstrate how CK2-mediated phosphorylation of two Hsp90 residues modulates virulence in a major fungal pathogen of humans, Candida albicans. We combined proteomics, molecular evolution and structural modelling with molecular biology to identify and characterize two Hsp90 phosphorylation sites. Phosphorylation negatively affects thermal stress response, morphogenesis, drug susceptibility and fungal virulence. Our results provide the first record of specific Hsp90 phosphorylation sites acting as modulators of fungal virulence. Post-translational modifications of Hsp90 could prove valuable in future exploitation as antifungal drug targets.

scholarly journals Test Antifungal Phatogen Extract Secondary Metabolites Of Endophytic Fungi Raru Plant (Cotylelobium melanoxylon)

2016 ◽  
Vol 1 (2) ◽  
pp. 6
Author(s):  
Uswatun Hasanah ◽  
Riwayati Riwayati ◽  
Idramsa Idramsa
Keyword(s):  
Candida Albicans ◽  
Secondary Metabolites ◽  
Endophytic Fungi ◽  
Fungal Pathogens ◽  
Pathogenic Fungus ◽  
Sclerotium Rolfsii ◽  
Pathogenic Fungi ◽  
Inhibition Zone ◽  
Clear Zone ◽  
Paper Disc

This study aims to determine the ability of extracts  secondary metabolites of endophytic fungi raru plant Siarang (Cotylelobium melanoxylon) in inhibiting the growth of pathogenic fungi. Pathogenic fungi tested were Collectotrichum, Fusarium oxysporum, Candida albicans and Sclerotium rolfsii. Test antifungal pathogens carried out by using the method of Kirby-Bour, ie by measuring the clear zone located around the paper disc which is the zone of growth inhibition of pathogenic fungi. Measurement of inhibition zone is done by using a caliper or ruler. The results showed that the secondary metabolites of endophytic fungi extracts could inhibit the growth of pathogenic fungus Candida albicans is the clear zone of 10.23 mm. Keywords : endophytic fungus, Cotylelobium melanoxylon, extract of secondary metabolites, fungal pathogens, inhibition zone

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