scholarly journals Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

2007 ◽  
Vol 71 (2) ◽  
pp. 348-376 ◽  
Author(s):  
Subhrajit Biswas ◽  
Patrick Van Dijck ◽  
Asis Datta
Keyword(s):  
Signal Transduction ◽  
Candida Albicans ◽  
Morphological Plasticity ◽  
Signal Transduction Pathways ◽  
Mycelial Form ◽  
Healthy Humans ◽  
Life Threatening ◽  
Opportunistic Fungal Pathogen ◽  
Reversible Transitions ◽  
Hyphal Formation

SUMMARY Candida albicans is an opportunistic fungal pathogen that is found in the normal gastrointestinal flora of most healthy humans. However, under certain environmental conditions, it can become a life-threatening pathogen. The shift from commensal organism to pathogen is often correlated with the capacity to undergo morphogenesis. Indeed, under certain conditions, including growth at ambient temperature, the presence of serum or N-acetylglucosamine, neutral pH, and nutrient starvation, C. albicans can undergo reversible transitions from the yeast form to the mycelial form. This morphological plasticity reflects the interplay of various signal transduction pathways, either stimulating or repressing hyphal formation. In this review, we provide an overview of the different sensing and signaling pathways involved in the morphogenesis and pathogenesis of C. albicans. Where appropriate, we compare the analogous pathways/genes in Saccharomyces cerevisiae in an attempt to highlight the evolution of the different components of the two organisms. The downstream components of these pathways, some of which may be interesting antifungal targets, are also discussed.

scholarly journals Interactions between Candida albicans and Enterococcus faecalis in an Organotypic Oral Epithelial Model

2020 ◽  
Vol 8 (11) ◽  
pp. 1771
Author(s):  
Akshaya Lakshmi Krishnamoorthy ◽  
Alex A. Lemus ◽  
Adline Princy Solomon ◽  
Alex M. Valm ◽  
Prasanna Neelakantan
Keyword(s):  
Candida Albicans ◽  
Enterococcus Faecalis ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Surface Erosion ◽  
Host Immune System ◽  
Microbial Invasion ◽  
Mucosal Surfaces ◽  
Life Threatening ◽  
Hyphal Formation

Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause oral and disseminated infections. Similar to C. albicans, Enterococcus faecalis is a major opportunistic pathogen, which is of critical concern in immunocompromised patients. There is increasing evidence that E. faecalis co-exists with C. albicans in the human body in disease samples. While the interactive profiles between these two organisms have been studied on abiotic substrates and mouse models, studies on their interactions on human oral mucosal surfaces are non-existent. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and P52S) on an organotypic oral mucosal model. Our results demonstrated that the dual species biofilms resulted in profound surface erosion and significantly increased microbial invasion into mucosal compartments, compared to either species alone. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. By contrast, E. faecalis genes involved in quorum sensing, biofilm formation, virulence, and mammalian cell invasion were downregulated. This study highlights the synergistic cross-kingdom interactions between E. faecalis and C. albicans in mucosal tissue invasion.

scholarly journals Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection

2002 ◽  
Vol 70 (2) ◽  
pp. 921-927 ◽  
Author(s):  
Peter Staib ◽  
Marianne Kretschmar ◽  
Thomas Nichterlein ◽  
Herbert Hof ◽  
Joachim Morschhäuser
Keyword(s):  
Signal Transduction ◽  
Candida Albicans ◽  
Genetic Recombination ◽  
Hyphal Growth ◽  
Transcriptional Regulators ◽  
Infected Tissue ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transduction Pathways ◽  
Aspartic Proteinases

ABSTRACT The opportunistic fungal pathogen Candida albicans can cause superficial as well as systemic infections. Successful adaptation to the different host niches encountered during infection requires coordinated expression of various virulence traits, including the switch between yeast and hyphal growth forms and secretion of aspartic proteinases. Using an in vivo expression technology that is based on genetic recombination as a reporter of gene activation during experimental candidiasis in mice, we investigated whether two signal transduction pathways controlling hyphal growth, a mitogen-activated protein kinase cascade ending in the transcriptional activator Cph1p and a cyclic AMP-dependent regulatory pathway that involves the transcription factor Efg1p, also control expression of the SAP5 gene, which encodes one of the secreted aspartic proteinases and is induced by host signals soon after infection. Our results show that both transcriptional regulators are important for SAP5 activation in vivo. SAP5 expression was reduced in a cph1 mutant, although filamentous growth in infected tissue was not detectably impaired. SAP5 expression was also reduced, but not eliminated, in an efg1 null mutant, although this strain grew exclusively in the yeast form in infected tissue, demonstrating that in contrast to in vitro conditions, SAP5 activation during infection does not depend on growth of C. albicans in the hyphal form. In a cph1 efg1 double mutant, however, SAP5 expression in infected mice was almost completely eliminated, suggesting that the two signal transduction pathways are important for SAP5 expression in vivo. The avirulence of the cph1 efg1 mutant seemed to be caused not only by the inability to form hyphae but also by a loss of expression of additional virulence genes in the host.

scholarly journals Mucins Suppress Virulence Traits of Candida albicans

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Nicole L. Kavanaugh ◽  
Angela Q. Zhang ◽  
Clarissa J. Nobile ◽  
Alexander D. Johnson ◽  
Katharina Ribbeck
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Therapeutic Potential ◽  
Content Type ◽  
Environmental Signals ◽  
Healthy Humans ◽  
Normal Microbiota ◽  
Life Threatening ◽  
Main Components

ABSTRACTCandida albicansis the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic invasions. Mucus, the gel that coats all wet epithelial surfaces, accommodatesC. albicansas part of the normal microbiota, whereC. albicansresides asymptomatically in healthy humans. Through a series ofin vitroexperiments combined with gene expression analysis, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology inC. albicansin which a range of genes related to adhesion, filamentation, and biofilm formation are downregulated. We also show that corresponding traits are suppressed, renderingC. albicansimpaired in forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggest that mucins can manipulateC. albicansphysiology, and we hypothesize that they are key environmental signals for retainingC. albicansin the host-compatible, commensal state.IMPORTANCEThe yeastCandida albicanscauses both superficial infections of the mucosa and life-threatening infections upon entering the bloodstream. However,C. albicansis not always harmful and can exist as part of the normal microbiota without causing disease. Internal body surfaces that are susceptible to infection byC. albicansare coated with mucus, which we hypothesize plays an important role in preventing infections. Here, we show that the main components of mucus, mucin glycoproteins, suppress virulence attributes ofC. albicansat the levels of gene expression and the corresponding morphological traits. Specifically, mucins suppress attachment to plastic surfaces and human cells, the transition to cell-penetrating hyphae, and the formation of biofilms (drug-resistant microbial communities). Additionally, exposure to mucins induces an elongated morphology that physically resembles the mating-competent opaque state but is phenotypically distinct. We suggest that mucins are potent antivirulence molecules that have therapeutic potential for suppressingC. albicansinfections.

scholarly journals Tec1 Mediates the Pheromone Response of the White Phenotype of Candida albicans: Insights into the Evolution of New Signal Transduction Pathways

PLoS Biology ◽  
2010 ◽  
Vol 8 (5) ◽  
pp. e1000363 ◽  
Author(s):  
Nidhi Sahni ◽  
Song Yi ◽  
Karla J. Daniels ◽  
Guanghua Huang ◽  
Thyagarajan Srikantha ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Candida Albicans ◽  
Signal Transduction Pathways ◽  
Pheromone Response
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