scholarly journals Faculty Opinions recommendation of Bacteria Modify Candida albicans Hypha Formation, Microcolony Properties, and Survival within Macrophages.

2020 ◽  
Author(s):  
Judith Berman ◽  
Lee Schnaider
Keyword(s):  
Candida Albicans ◽  
Hypha Formation

scholarly journals Bacteria Modify Candida albicans Hypha Formation, Microcolony Properties, and Survival within Macrophages

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Ornella Salvatori ◽  
Rohitashw Kumar ◽  
Sarah Metcalfe ◽  
Margaret Vickerman ◽  
Jason G. Kay ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Innate Immune ◽  
Phagocytic Cells ◽  
Content Type ◽  
Floating Structures ◽  
Epithelial Monolayers ◽  
Hypha Formation ◽  
Signaling Peptides ◽  
Culture Supernatants ◽  
Phagocytic Killing

ABSTRACT Phagocytic cells are crucial components of the innate immune system preventing Candida albicans mucosal infections. Streptococcus gordonii and Pseudomonas aeruginosa often colonize mucosal sites, along with C. albicans, and yet interkingdom interactions that might alter the survival and escape of fungi from macrophages are not understood. Murine macrophages were coinfected with S. gordonii or P. aeruginosa, along with C. albicans to evaluate changes in fungal survival. S. gordonii increased C. albicans survival and filamentation within macrophage phagosomes, while P. aeruginosa reduced fungal survival and filamentation. Coinfection with S. gordonii resulted in greater escape of C. albicans from macrophages and increased size of fungal microcolonies formed on macrophage monolayers, while coinfection with P. aeruginosa reduced macrophage escape and produced smaller microcolonies. Microcolonies formed in the presence of P. aeruginosa cells outside macrophages also had significantly reduced size that was not found with P. aeruginosa phenazine deletion mutants. S. gordonii cells, as well as S. gordonii heat-fixed culture supernatants, increased C. albicans microcolony biomass but also resulted in microcolony detachment. A heat-resistant, trypsin-sensitive pheromone processed by S. gordonii Eep was needed for these effects. The majority of fungal microcolonies formed on human epithelial monolayers with S. gordonii supernatants developed as large floating structures with no detectable invasion of epithelium, along with reduced gene expression of C. albicans HYR1, EAP1, and HWP2 adhesins. However, a subset of C. albicans microcolonies was smaller and had greater epithelial invasiveness compared to microcolonies grown without S. gordonii. Thus, bacteria can alter the killing and escape of C. albicans from macrophages and contribute to changes in C. albicans pathogenicity. IMPORTANCE Candida albicans is the predominant fungus colonizing the oral cavity that can have both synergistic and antagonistic interactions with other bacteria. Interkingdom polymicrobial associations modify fungal pathogenicity and are believed to increase microbial resistance to innate immunity. However, it is not known how these interactions alter fungal survival during phagocytic killing. We demonstrated that secreted molecules of S. gordonii and P. aeruginosa alter C. albicans survival within the phagosome of macrophages and alter fungal pathogenic phenotypes, including filamentation and microcolony formation. Moreover, we provide evidence for a dual interaction between S. gordonii and C. albicans such that S. gordonii signaling peptides can promote C. albicans commensalism by decreasing microcolony attachment while increasing invasion in epithelial cells. Our results identify bacterial diffusible factors as an attractive target to modify virulence of C. albicans in polymicrobial infections.

scholarly journals Disparate Candida albicans Biofilm Formation in Clinical Lipid Emulsions Due to Capric Acid-Mediated Inhibition

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Hubertine M. E. Willems ◽  
Jeremy S. Stultz ◽  
Molly E. Coltrane ◽  
Jabez P. Fortwendel ◽  
Brian M. Peters
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Bloodstream Infections ◽  
Capric Acid ◽  
Lipid Emulsions ◽  
Biofilm Growth ◽  
Content Type ◽  
Biofilm Model ◽  
Hypha Formation

ABSTRACT Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN solutions contain lipid emulsions to supply daily essential fats and are often delivered via central venous catheters (CVCs). Therefore, using an in vitro biofilm model system, we sought to determine whether various clinical lipid emulsions differentially impacted biofilm growth in C. albicans. We observed that the lipid emulsions Intralipid and Omegaven both stimulated C. albicans biofilm formation during growth in minimal medium or a macronutrient PN solution. Conversely, Smoflipid inhibited C. albicans biofilm formation by approximately 50%. Follow-up studies revealed that while Smoflipid did not impair C. albicans growth, it did significantly inhibit hypha formation and hyphal elongation. Moreover, growth inhibition could be recapitulated in Intralipid when supplemented with capric acid—a fatty acid present in Smoflipid but absent in Intralipid. Capric acid was also found to dose dependently inhibit C. albicans biofilm formation in PN solutions. This is the first study to directly compare different clinical lipid emulsions for their capacity to affect C. albicans biofilm growth. Results derived from this study necessitate further research regarding different lipid emulsions and rates of fungus-associated CR-BSIs.

scholarly journals Zap1 Control of Cell-Cell Signaling in Candida albicans Biofilms

2011 ◽  
Vol 10 (11) ◽  
pp. 1448-1454 ◽  
Author(s):  
Shantanu Ganguly ◽  
Andrew C. Bishop ◽  
Wenjie Xu ◽  
Suman Ghosh ◽  
Kenneth W. Nickerson ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Yeast Cells ◽  
Gas Chromatography Mass Spectrometry ◽  
Wild Type ◽  
Content Type ◽  
Reverse Transcription Pcr ◽  
Hypha Formation ◽  
Dependent Signal ◽  
Reporter Strains ◽  
Biosensor Strain

ABSTRACTBiofilms ofCandida albicansinclude both yeast cells and hyphae. Prior studies indicated that azap1Δ/Δ mutant, defective in zinc regulator Zap1, has increased accumulation of yeast cells in biofilms. This altered yeast-hypha balance may arise from internal regulatory alterations or from an effect on the production of diffusible quorum-sensing (QS) molecules. Here, we develop biosensor reporter strains that express yeast-specificYWP1-RFPor hypha-specificHWP1-RFP, along with a constitutiveTDH3-GFPnormalization standard. Seeding these biosensor strains into biofilms allows a biological activity assay of the surrounding biofilm milieu. Azap1Δ/Δ biofilm induces the yeast-specificYWP1-RFPreporter in a wild-type biosensor strain, as determined by both quantitative reverse transcription-PCR (qRT-PCR) gene expression measurements and confocal microscopy. Remediation of thezap1Δ/Δ zinc uptake defect through zinc transporter geneZRT2overexpression reverses induction of the yeast-specificYWP1-RFPreporter. Gas chromatography-mass spectrometry (GC-MS) measurements of known organic QS molecules show that thezap1Δ/Δ mutant accumulates significantly less farnesol than wild-type or complemented strains and thatZRT2overexpression does not affect farnesol accumulation. Farnesol is a well-characterized inhibitor of hypha formation; hence, a reduction in farnesol levels inzap1Δ/Δ biofilms is unexpected. Our findings argue that a Zap1- and zinc-dependent signal affects the yeast-hypha balance and that it is operative in the low-farnesol environment of thezap1Δ/Δ biofilm. In addition, our results indicate that Zap1 is a positive regulator of farnesol accumulation.

Carbon source induced yeast-to-hypha transition in Candida albicans is dependent on the presence of amino acids and on the G-protein-coupled receptor Gpr1

2005 ◽  
Vol 33 (1) ◽  
pp. 291-293 ◽  
Author(s):  
M.M. Maidan ◽  
J.M. Thevelein ◽  
P. Van Dijck
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Candida Albicans ◽  
Carbon Source ◽  
G Protein ◽  
High Glucose ◽  
Glucose Concentration ◽  
G Protein Coupled Receptor ◽  
Hypha Formation ◽  
G Protein Coupled

Yeast-to-hypha transition in Candida albicans can be induced by a wide variety of factors, including specific nutrients. We have started to investigate the mechanism by which some of these nutrients may be sensed. The G-protein-coupled receptor Gpr1 is required for yeast-to-hypha transition on various solid hypha-inducing media. Recently we have shown induction of Gpr1 internalization by specific amino acids, e.g. methionine. This suggests a possible role for methionine as a ligand of CaGpr1. Here we show that there is a big variation in methionine-induced hypha formation depending on the type of carbon source present in the medium. In addition high glucose concentrations repress hypha formation whereas a concentration of 0.1%, which mimics the glucose concentration present in the bloodstream, results in maximal hypha formation. Hence, it remains unclear whether Gpr1 senses sugars, as in Saccharomyces cerevisiae, or specific amino acids like methionine.

scholarly journals Sep7 Is Essential to Modify Septin Ring Dynamics and Inhibit Cell Separation during Candida albicans Hyphal Growth

2008 ◽  
Vol 19 (4) ◽  
pp. 1509-1518 ◽  
Author(s):  
Alberto González-Novo ◽  
Jaime Correa-Bordes ◽  
Leticia Labrador ◽  
Miguel Sánchez ◽  
Carlos R. Vázquez de Aldana ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Separation ◽  
Hyphal Growth ◽  
Yeast Cells ◽  
Septin Ring ◽  
Protein Levels ◽  
Hyphal Morphogenesis ◽  
Hypha Formation ◽  
Ring Dynamics ◽  
Cytoskeleton Dynamics

When Candida albicans yeast cells receive the appropriate stimulus, they switch to hyphal growth, characterized by continuous apical elongation and the inhibition of cell separation. The molecular basis of this inhibition is poorly known, despite its crucial importance for hyphal development. In C. albicans, septins are important for hypha formation and virulence. Here, we used fluorescence recovery after photobleaching analysis to characterize the dynamics of septin rings during yeast and hyphal growth. On hyphal induction, septin rings are converted to a hyphal-specific state, characterized by the presence of a frozen core formed by Sep7/Shs1, Cdc3 and Cdc12, whereas Cdc10 is highly dynamic and oscillates between the ring and the cytoplasm. Conversion of septin rings to the hyphal-specific state inhibits the translocation of Cdc14 phosphatase, which controls cell separation, to the hyphal septum. Modification of septin ring dynamics during hyphal growth is dependent on Sep7 and the hyphal-specific cyclin Hgc1, which partially controls Sep7 phosphorylation status and protein levels. Our results reveal a link between the cell cycle machinery and septin cytoskeleton dynamics, which inhibits cell separation in the filaments and is essential for hyphal morphogenesis.

scholarly journals Disruption of the Candida albicans TPS2 Gene Encoding Trehalose-6-Phosphate Phosphatase Decreases Infectivity without Affecting Hypha Formation

2002 ◽  
Vol 70 (4) ◽  
pp. 1772-1782 ◽  
Author(s):  
Patrick Van Dijck ◽  
Larissa De Rop ◽  
Karolina Szlufcik ◽  
Elke Van Ael ◽  
Johan M. Thevelein
Keyword(s):  
Candida Albicans ◽  
High Throughput Screening ◽  
Deletion Mutant ◽  
Systemic Infection ◽  
Homozygous Deletion ◽  
Antifungal Drugs ◽  
Gene Encoding ◽  
Complete Inactivation ◽  
Hypha Formation ◽  
Stress Protectant

ABSTRACT Deletion of trehalose-6-phosphate phosphatase, encoded by TPS2, in Saccharomyces cerevisiae results in accumulation of trehalose-6-phosphate (Tre6P) instead of trehalose under stress conditions. Since trehalose is an important stress protectant and Tre6P accumulation is toxic, we have investigated whether Tre6P phosphatase could be a useful target for antifungals in Candida albicans. We have cloned the C. albicans TPS2 (CaTPS2) gene and constructed heterozygous and homozygous deletion strains. As in S. cerevisiae, complete inactivation of Tre6P phosphatase in C. albicans results in 50-fold hyperaccumulation of Tre6P, thermosensitivity, and rapid death of the cells after a few hours at 44°C. As opposed to inactivation of Tre6P synthase by deletion of CaTPS1, deletion of CaTPS2 does not affect hypha formation on a solid glucose-containing medium. In spite of this, virulence of the homozygous deletion mutant is strongly reduced in a mouse model of systemic infection. The pathogenicity of the heterozygous deletion mutant is similar to that of the wild-type strain. CaTPS2 is a new example of a gene not required for growth under standard conditions but required for pathogenicity in a host. Our results suggest that Tre6P phosphatase may serve as a potential target for antifungal drugs. Neither Tre6P phosphatase nor its substrate is present in mammals, and assay of the enzymes is simple and easily automated for high-throughput screening.

scholarly journals Functional Mapping of the Candida albicans Efg1 Regulator

2008 ◽  
Vol 7 (5) ◽  
pp. 881-893 ◽  
Author(s):  
Christine S. Noffz ◽  
Vanessa Liedschulte ◽  
Klaus Lengeler ◽  
Joachim F. Ernst
Keyword(s):  
Candida Albicans ◽  
Dna Binding ◽  
Protein Interactions ◽  
Functional Domains ◽  
Helix Loop Helix ◽  
Hypha Formation ◽  
Flanking Sequences ◽  
Flanking Regions ◽  
Two Hybrid ◽  
Repressor Activity

ABSTRACT Efg1p is a key transcriptional regulator in Candida albicans which controls various aspects of morphogenesis and metabolism in this organism. Efg1p contains a central basic helix-loop-helix (bHLH) domain, flanked by sequences highly conserved in fungal APSES proteins, as well as polyglutamine stretches at the N- and C-terminal ends. A systematic deletion approach to specify functional domains of Efg1p revealed that the APSES domain is essential for morphogenesis of the normal yeast and true hyphal cell forms and that bHLH flanking sequences are needed for Efg1p stability. Additional C-terminal sequences were required for hypha formation on some inducing media, and most Efg1p sequences were needed for chlamydospore morphogenesis. Overexpression of EFG1 led to pseudohypha formation only if a functional APSES domain was present, while a switch from the opaque to the white cell type in addition depended on the presence of certain N- and C-terminal segments. Yeast two-hybrid experiments revealed that binding of Efg1p to its antagonist Czf1p required two regions outside of the APSES domain, which did not coincide with Efg1p sequences needed for its transcriptional repressor activity. Binding of the Flo8 transcription factor to Efg1p did not require the APSES domain but appeared to occur at two or more redundant domains. In contrast, DNA binding of Efg1p to an MluI cell cycle box (MCB) element solely required the APSES domain. Overall, these results suggest that functional domains of Efg1p are spread throughout most of its sequences, including the central APSES domain involved in DNA binding, as well as flanking regions required for various protein interactions and regulatory activities.

scholarly journals Sch9 Kinase Integrates Hypoxia and CO2Sensing To Suppress Hyphal Morphogenesis in Candida albicans

2011 ◽  
Vol 10 (4) ◽  
pp. 502-511 ◽  
Author(s):  
Catrin Stichternoth ◽  
Alida Fraund ◽  
Eleonora Setiadi ◽  
Luc Giasson ◽  
Anna Vecchiarelli ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Wild Type Strain ◽  
Cell Wall Proteins ◽  
Content Type ◽  
Chronological Aging ◽  
Hyphal Morphogenesis ◽  
Hypha Formation ◽  
Virulence Trait ◽  
Genes Encoding ◽  
A Minor

ABSTRACTThe yeast-hypha transition is an important virulence trait ofCandida albicans. We report that the AGC kinase Sch9 prevents hypha formation specifically under hypoxia at high CO2levels.sch9mutants showed no major defects in growth and stress resistance but a striking hyperfilamentous phenotype under hypoxia (<10% O2), although only in the presence of elevated CO2levels (>1%) and at temperatures of <37°C during surface growth. Thesch9hyperfilamentous phenotype was independent of Rim15 kinase and was recreated by inhibition of Tor1 kinase by rapamycin or caffeine in a wild-type strain, suggesting that Sch9 suppression requires Tor1. Caffeine inhibition also revealed that both protein kinase A isoforms, as well as transcription factors Czf1 and Ace2, are required to generate thesch9mutant phenotype. Transcriptomal analyses showed that Sch9 regulates most genes solely under hypoxia and in the presence of elevated CO2. In this environment, Sch9 downregulates genes encoding cell wall proteins and nutrient transporters, while under normoxia Sch9 and Tor1 coregulate a minor fraction of Sch9-regulated genes, e.g., by inducing glycolytic genes. Other than inSaccharomyces cerevisiae, bothsch9andrim15mutants showed decreased chronological aging under normoxia but not under hypoxia, indicating significant rewiring of the Tor1-Sch9-Rim15 pathway inC. albicans. The results stress the importance of environmental conditions on Sch9 function and establish a novel response circuitry to both hypoxia and CO2inC. albicans, which suppresses hypha formation but also allows efficient nutrient uptake, metabolism, and virulence.

scholarly journals Hyphal Tip-Associated Localization of Cdc42 Is F-Actin Dependent in Candida albicans

2002 ◽  
Vol 1 (6) ◽  
pp. 856-864 ◽  
Author(s):  
Idit Hazan ◽  
Haoping Liu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Green Fluorescence Protein ◽  
Neck Region ◽  
Eukaryotic Cell ◽  
Yeast Form ◽  
Hypha Formation ◽  
Nuclear Separation ◽  
Bud Site ◽  
Hyphal Tip

ABSTRACT The rho-type GTPase Cdc42 is important for the establishment and maintenance of eukaryotic cell polarity. To examine whether Cdc42 is regulated during the yeast-to-hypha transition in Candida albicans, we constructed a green fluorescence protein (GFP)-Cdc42 fusion under the ACT1 promoter and observed its localization in live C. albicans cells. As in Saccharomyces cerevisiae, GFP-Cdc42 was observed around the entire periphery of the cell. In yeast-form cells of C. albicans, it clustered to the tips and sides of small buds as well as to the mother-daughter neck region of large-budded cells. Upon hyphal induction, GFP-Cdc42 clustered to the site of hyphal evagination and remained at the tips of the hyphae. This temporal and spatial localization of Cdc42 suggests that its activity is regulated during the yeast-to-hypha transition. In addition to the accumulation at the hyphal tip, GFP-Cdc42 was also seen as a band within the hyphal tube in cells that had undergone nuclear separation. With the F-actin-assembly inhibitor latrunculin A, we found that GFP-Cdc42 accumulation at the bud site in yeast-form cells is F-actin independent, whereas GFP-Cdc42 accumulation at the hyphal tip requires F-actin. Furthermore, disruption of the F-actin cytoskeleton impaired the transcriptional induction of hypha-specific genes. Therefore, hypha formation resembles mating in Saccharomyces cerevisiae in that both require F-actin for GFP-Cdc42 localization and efficient signaling.

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