scholarly journals Control of β-glucan exposure by the endo-1,3-glucanase Eng1 in Candida albicans modulates virulence

2020 ◽  
Author(s):  
Mengli Yang ◽  
Norma V. Solis ◽  
Michaela Marshall ◽  
Rachel Garleb ◽  
Tingting Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Innate Immune Response ◽  
Type Strain ◽  
Wild Type Strain ◽  
Innate Immune ◽  
Yeast Cells ◽  
Parallel Mechanisms ◽  
Wild Type ◽  
Lectin Receptor

AbstractCandida albicans is a major cause of invasive candidiasis, which has a high mortality rate. The hyphal form of C. albicans is virulent and activates the host innate immune response, while the yeast form is hypovirulent and less immunogenic. The innate immune response is critical for host defense, but overactivation can cause tissue damage and sepsis. The innate immune response can be triggered when the C-type lectin receptor Dectin-1 recognizes β-glucans, which is protected by the outer mannan layer of the cell wall on C. albicans. Here, we demonstrate that there is low level of Dectin-1 binding at the septum of yeast cells, but high level of Dectin-1 binding over the entire surface of hyphae. We find that β-glucan masking in yeast is controlled by two highly expressed yeast proteins, the endo-1,3-β-glucanase Eng1 and the Yeast Wall Protein Ywp1. An eng1 deletion mutant shows enhanced Dectin-1 binding at the septa, while an eng1 ywp1 double mutant, but not an ywp1 single mutant, shows strong overall Dectin-1 binding. Thus, Eng1-mediated β-glucan trimming and Ywp1-mediated β-glucan masking are two parallel mechanisms utilized by C. albicans yeast to minimize recognition by Dectin-1. In the model of disseminated candidiasis, mice infected with the eng1 deletion mutant showed delayed mortality with an increased renal immune response in males compared to mice infected with the wild-type strain, but earlier mortality with a higher renal immune response in females. Using the eng1 mutant that is specifically defective in β-glucan masking in yeast, this study demonstrates that the level of β-glucan exposure is important for modulating the balance between immune protection and immunopathogenesis.Abstract ImportanceCandida albicans is a major opportunistic fungal pathogen of humans. Systemic Candidiasis has high mortality rates. C. albicans is also a constituent of the human microbiome and found in gastrointestinal and genitourinary tracts of most healthy individuals. C. albicans is able to switch reversibly between yeast and hyphae in response to environmental cues. The hyphal form is virulent, while the yeast form is hypovirulent and less immunogenic. This study demonstrates that β-glucan exposure in yeast is protected by two highly expressed yeast proteins, the endo-1,3-β-glucanase Eng1 and the Yeast Wall Protein Ywp1. Eng1-mediated β-glucan trimming and Ywp1-mediated β-glucan masking are two parallel mechanisms utilized by C. albicans yeast to minimize recognition by the host C-type lectin receptor Dectin-1. The eng1 mutant triggers a higher immune response and leads to earlier mortality compared to the wild-type strain. Thus, β-glucan masking in yeast keeps yeast cells less immunogenic and hypovirulent.

scholarly journals Candida albicans-Secreted Aspartic Proteinases Modify the Epithelial Cytokine Response in an In Vitro Model of Vaginal Candidiasis

2005 ◽  
Vol 73 (5) ◽  
pp. 2758-2765 ◽  
Author(s):  
Martin Schaller ◽  
Hans C. Korting ◽  
Claudia Borelli ◽  
Gerald Hamm ◽  
Bernhard Hube
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Proteinase Inhibitor ◽  
Type Strain ◽  
Wild Type Strain ◽  
Cytokine Expression ◽  
Cytokine Response ◽  
Vaginal Candidiasis ◽  
Wild Type ◽  
Pepstatin A

ABSTRACT Secreted aspartyl proteinases (Saps) are important virulence factors of Candida albicans during mucosal and disseminated infections and may also contribute to the induction of an inflammatory host immune response. We used a model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) to study the epithelial cytokine response induced by C. albicans. In order to study the impact of the overall proteolytic activity and of distinct Sap isoenzymes, we studied the effect of the proteinase inhibitor pepstatin A on the immune response and compared the cytokine expression pattern induced by the wild-type strain SC5314 with the pattern induced by Sap-deficient mutants. Infection of RHVE with the C. albicans wild-type strain induced strong interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha responses in comparison with cytokine expression in noninfected tissue. Addition of the aspartyl proteinase inhibitor pepstatin A strongly reduced the cytokine response of RHVE. Furthermore, SAP-null mutants lacking either SAP1 or SAP2 caused reduced tissue damage and had a significantly reduced potential to stimulate cytokine expression. In contrast, the vaginopathic and cytokine-inducing potential of mutants lacking SAP4 to SAP6 was similar to that of the wild-type strain. These data show that the potential of specific Saps to cause tissue damage correlates with an epithelium-induced proinflammatory cytokine response, which may be crucial in controlling and managing C. albicans infections at the vaginal mucosa in vivo.

scholarly journals CaNdt80 Is Involved in Drug Resistance in Candida albicans by Regulating CDR1

2004 ◽  
Vol 48 (12) ◽  
pp. 4505-4512 ◽  
Author(s):  
Chia-Geun Chen ◽  
Yun-Liang Yang ◽  
Hsin-I Shih ◽  
Chia-Li Su ◽  
Hsiu-Jung Lo
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Type Strain ◽  
Antifungal Agents ◽  
Wild Type Strain ◽  
Efflux Pump ◽  
Antifungal Drugs ◽  
Galactosidase Activity ◽  
Wild Type

ABSTRACT Overexpression of CDR1, an efflux pump, is one of the major mechanisms contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene could be used as the reporter to monitor the activity of the CDR1 promoter. Overexpression of CaNDT80, the C. albicans homolog of S. cerevisiae NDT80, increases the β-galactosidase activity of the CDR1 p-lacZ construct in S. cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1 expression by antifungal agents in C. albicans. Consistently, the Candt80/Candt80 mutant is also more susceptible to antifungal drugs than the wild-type strain. Thus, the gene for CaNdt80 may be the first gene among the regulatory factors involved in drug resistance in C. albicans whose function has been identified.

scholarly journals CpG Oligodeoxynucleotides Increase the Susceptibility of Normal Mice to Infection by Candida albicans

2005 ◽  
Vol 73 (9) ◽  
pp. 6154-6156 ◽  
Author(s):  
Shuichi Ito ◽  
Joao Pedras-Vasconcelos ◽  
Dennis M. Klinman
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Innate Immune Response ◽  
Host Resistance ◽  
Cytokine Production ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Motifs ◽  
Resistance To Infection

ABSTRACT Synthetic oligodeoxynucleotides containing CpG motifs trigger an innate immune response that typically increases host resistance to infection. Yet CpG treatment reduces the resistance of normal mice to Candida albicans infection. This effect is mediated by CpG-induced interleukin-12, indicating that CpG-dependent cytokine production may have adverse consequences for the host.

scholarly journals Sml1 Inhibits the DNA Repair Activity of Rev1 in Saccharomyces cerevisiae during Oxidative Stress

2020 ◽  
Vol 86 (7) ◽  
Author(s):  
Rui Yao ◽  
Pei Zhou ◽  
Chengjin Wu ◽  
Liming Liu ◽  
Jing Wu
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Survival Rate ◽  
Type Strain ◽  
Mutation Frequency ◽  
Wild Type Strain ◽  
Yeast Cells ◽  
Wild Type ◽  
Content Type

ABSTRACT In Saccharomyces cerevisiae, Y family DNA polymerase Rev1 is involved in the repair of DNA damage by translesion DNA synthesis (TLS). In the current study, to elucidate the role of Rev1 in oxidative stress-induced DNA damage in S. cerevisiae, REV1 was deleted and overexpressed; transcriptome analysis of these mutants along with the wild-type strain was performed to screen potential genes that could be associated with REV1 during response to DNA damage. When the yeast cells were treated with 2 mM H2O2, the deletion of REV1 resulted in a 1.5- and 2.8-fold decrease in the survival rate and mutation frequency, respectively, whereas overexpression of REV1 increased the survival rate and mutation frequency by 1.1- and 2.9-fold, respectively, compared to the survival rate and mutation frequency of the wild-type strain. Transcriptome and phenotypic analyses identified that Sml1 aggravated oxidative stress in the yeast cells by inhibiting the activity of Rev1. This inhibition was due to the physical interaction between the BRCA1 C terminus (BRCT) domain of Rev1 and amino acid residues 36 to 70 of Sml1; the cell survival rate and mutation frequency increased by 1.8- and 3.1-fold, respectively, when this interaction was blocked. We also found that Sml1 inhibited Rev1 phosphorylation under oxidative stress and that deletion of SML1 increased the phosphorylation of Rev1 by 46%, whereas overexpression of SML1 reduced phosphorylation of Rev1. Overall, these findings demonstrate that Sml1 could be a novel regulator that mediates Rev1 dephosphorylation to inhibit its activity during oxidative stress. IMPORTANCE Rev1 was critical for cell growth in S. cerevisiae, and the deletion of REV1 caused a severe growth defect in cells exposed to oxidative stress (2 mM H2O2). Furthermore, we found that Sml1 physically interacted with Rev1 and inhibited Rev1 phosphorylation, thereby inhibiting Rev1 DNA antioxidant activity. These findings indicate that Sml1 could be a novel regulator for Rev1 in response to DNA damage by oxidative stress.

scholarly journals Circulating γδ T Cells in Response to Salmonellaenterica Serovar Enteritidis Exposure in Chickens

2006 ◽  
Vol 74 (7) ◽  
pp. 3967-3978 ◽  
Author(s):  
Angela Berndt ◽  
Jana Pieper ◽  
Ulrich Methner
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Type Strain ◽  
Wild Type Strain ◽  
Γδ T Cells ◽  
Immunohistochemical Analysis ◽  
Wild Type ◽  
Γδt Cells

ABSTRACT γδT cells are considered crucial to the outcome of various infectious diseases. The present study was undertaken to characterizeγδ (T-cell receptor 1+ [TCR1+]) T cells phenotypically and functionally in avian immune response. Day-old chicks were orally immunized with Salmonella enterica serovar Enteritidis live vaccine or S. enterica serovar Enteritidis wild-type strain and infected using the S. enterica serovar Enteritidis wild-type strain on day 44 of life. Between days 3 and 71, peripheral blood was examined flow cytometrically for the occurrence of γδ T-cell subpopulations differentiated by the expression of T-cell antigens. Three different TCR1+ cell populations were found to display considerable variation regarding CD8α antigen expression: (i) CD8α+high TCR1+ cells, (ii) CD8α+dim TCR1+ cells, and (iii) CD8α− TCR1+ cells. While most of the CD8α+high TCR1+ cells expressed the CD8αβ heterodimeric antigen, the majority of the CD8α+dim TCR1+ cells were found to express the CD8αα homodimeric form. After immunization, a significant increase of CD8αα+high γδ T cells was observed within the CD8α+high TCR1+ cell population. Quantitative reverse transcription-PCR revealed reduced interleukin-7 receptor α (IL-7Rα) and Bcl-x expression and elevated IL-2Rα mRNA expression of the CD8αα+highγδ T cells. Immunohistochemical analysis demonstrated a significant increase of CD8α+ and TCR1+ cells in the cecum and spleen and a decreased percentage of CD8β+ T cells in the spleen after Salmonella immunization. After infection of immunized animals, immune reactions were restricted to intestinal tissue. The study showed that Salmonella immunization of very young chicks is accompanied by an increase of CD8αα+high γδ T cells in peripheral blood, which are probably activated, and thus represent an important factor for the development of a protective immune response to Salmonella organisms in chickens.

scholarly journals Correction to: Effect of 1064-nm Q-switched Nd:YAG laser on invasiveness and innate immune response in keratinocytes infected with Candida albicans

2018 ◽  
Vol 33 (3) ◽  
pp. 691-691
Author(s):  
Adone Baroni ◽  
Anna De Filippis ◽  
Giovanni Oliviero ◽  
Alessandra Fusco ◽  
Brunella Perfetto ◽  
...  
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Innate Immune Response ◽  
Nd:Yag Laser ◽  
Innate Immune

scholarly journals Role of Calcineurin in Stress Resistance, Morphogenesis, and Virulence of a Candida albicans Wild-Type Strain

2006 ◽  
Vol 74 (7) ◽  
pp. 4366-4369 ◽  
Author(s):  
Teresa Bader ◽  
Klaus Schröppel ◽  
Stefan Bentink ◽  
Nina Agabian ◽  
Gerwald Köhler ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Type Strain ◽  
Pulmonary Infection ◽  
Wild Type Strain ◽  
Selection Marker ◽  
Wild Type ◽  
Environmental Signals ◽  
Successful Infection ◽  
Strain Sc5314

ABSTRACT By generating a calcineurin mutant of the Candida albicans wild-type strain SC5314 with the help of a new recyclable dominant selection marker, we confirmed that calcineurin mediates tolerance to a variety of stress conditions but is not required for the ability of C. albicans to switch to filamentous growth in response to hypha-inducing environmental signals. While calcineurin was essential for virulence of C. albicans in a mouse model of disseminated candidiasis, deletion of CMP1 did not significantly affect virulence during vaginal or pulmonary infection, demonstrating that the requirement for calcineurin for a successful infection depends on the host niche.

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