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Overview
No description specified

Programme: Collaborative Research Center / Transregio 124 "Pathogenic fungi and their human host: Networks of Interaction - FungiNet"

SEEK ID: https://funginet.hki-jena.de/projects/11

Public web page: http://www.funginet.de/home.html

Organisms: Aspergillus fumigatus, Candida albicans

INF PALs: No PALs for this Project

Project created: 1st Oct 2012

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26 hidden items
5th Joint Meeting IMIHM XII & CRC/TR 124
FungiNet total

Programme

Creators: Thomas Wolf, Jürgen Löffler, Annika Tittelbach-Helmrich

Contributor: Thomas Wolf

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DMykG 2015 Programmheft
FungiNet total, FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, FungiNet C - Candida projects, INF, Z2
No description specified

Creator: Reinhard Guthke

Contributor: Reinhard Guthke

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DMykG_2015 Programmheft
FungiNet total, FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, FungiNet C - Candida projects, INF, Z2
No description specified

Creator: Reinhard Guthke

Contributor: Reinhard Guthke

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Annual Meeting CRC/TR 124 FungiNet - 2014 - Program
FungiNet total
No description specified

Creator: Reinhard Guthke

Contributor: Reinhard Guthke

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Sample File "FungiNet_template_RNA-seq_V1.9_Ex_ID_005"
FungiNet total, A1

Cultivation of A. fumigatus in an O2-controlled fermenter and analysed its minute-scale responses to O2 limitation. Transcriptome sequencing revealed a group of genes underlying a rapid and highly dynamic regulation.

Creators: Jörg Linde, Falk Hillmann, Olaf Kniemeyer

Contributor: Maja Rey

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[DEMO] Response of hepatocytes to rapid change in the medium composition (gene regulatory network): Model 1100 "freshMedia"
FungiNet total, FungiNet B - Bioinformatics projects

Primary hepatocytes were exposed to a stimulus by exchanging culture medium, thereby simulating changes in the blood composition. The expression of genes at different time points was recorded. Differentially expressed genes were clustered using fuzzy c-means algorithm into five groups. The arcs of the possible network were identified using the NetGenerator algorithm under the restriction of biological knowledge. The analysis was restricted to the main metabolic pathways of hepatocytes. The reverse
...

Creators: Thomas Wolf, Wolfgang Schmidt-Heck, Reinhard Guthke

Contributor: Thomas Wolf

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Proteome Analysis Reveals the Conidial Surface Protein CcpA Essential for Virulence of the Pathogenic Fungus Aspergillus fumigatus.
FungiNet total, Z2

Abstract (Expand)

Aspergillus fumigatus is a common airborne fungal pathogen of humans and a significant source of mortality in immunocompromised individuals. Here, we provide the most extensive cell wall proteome … profiling to date of A. fumigatus resting conidia, the fungal morphotype pertinent to first contact with the host. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified proteins within the conidial cell wall by hydrogen-fluoride (HF)-pyridine extraction and proteins exposed on the surface using a trypsin-shaving approach. One protein, designated conidial cell wall protein A (CcpA), was identified by both methods and was found to be nearly as abundant as hydrophobic rodlet layer-forming protein RodA. CcpA, an amphiphilic protein, like RodA, peaks in expression during sporulation on resting conidia. Despite high cell wall abundance, the cell surface structure of DeltaccpA resting conidia appeared normal. However, trypsin shaving of DeltaccpA conidia revealed novel surface-exposed proteins not detected on conidia of the wild-type strain. Interestingly, the presence of swollen DeltaccpA conidia led to higher activation of neutrophils and dendritic cells than was seen with wild-type conidia and caused significantly less damage to epithelial cells in vitro In addition, virulence was highly attenuated when cortisone-treated, immunosuppressed mice were infected with DeltaccpA conidia. CcpA-specific memory T cell responses were detectable in healthy human donors naturally exposed to A. fumigatus conidia, suggesting a role for CcpA as a structural protein impacting conidial immunogenicity rather than possessing a protein-intrinsic immunosuppressive effect. Together, these data suggest that CcpA serves as a conidial stealth protein by altering the conidial surface structure to minimize innate immune recognition.IMPORTANCE The mammalian immune system relies on recognition of pathogen surface antigens for targeting and clearance. In the absence of immune evasion strategies, pathogen clearance is rapid. In the case of Aspergillus fumigatus, the successful fungus must avoid phagocytosis in the lung to establish invasive infection. In healthy individuals, fungal spores are cleared by immune cells; however, in immunocompromised patients, clearance mechanisms are impaired. Here, using proteome analyses, we identified CcpA as an important fungal spore protein involved in pathogenesis. A. fumigatus lacking CcpA was more susceptible to immune recognition and prompt eradication and, consequently, exhibited drastically attenuated virulence. In infection studies, CcpA was required for virulence in infected immunocompromised mice, suggesting that it could be used as a possible immunotherapeutic or diagnostic target in the future. In summary, our report adds a protein to the list of those known to be critical to the complex fungal spore surface environment and, more importantly, identifies a protein important for conidial immunogenicity during infection.

Authors: V. Voltersen, M. G. Blango, S. Herrmann, F. Schmidt, Thorsten Heinekamp, M. Strassburger, Thomas Krüger, P. Bacher, Jasmin Lother, Esther Weiß, Kerstin Hünniger, H. Liu, P. Hortschansky, A. Scheffold, Jürgen Löffler, S. Krappmann, S. Nietzsche, Oliver Kurzai, Hermann Einsele, Olaf Kniemeyer, S. G. Filler, U. Reichard, Axel Brakhage

Date Published: No date defined

Journal: MBio

Carbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreA.
FungiNet total, A1, Z2

Abstract (Expand)

Filamentous fungi of the genus Aspergillus are of particular interest for biotechnological applications due to their natural capacity to secrete carbohydrate-active enzymes (CAZy) that target plant … biomass. The presence of easily metabolizable sugars such as glucose, whose concentrations increase during plant biomass hydrolysis, results in the repression of CAZy-encoding genes in a process known as carbon catabolite repression (CCR), which is undesired for the purpose of large-scale enzyme production. To date, the C2H2 transcription factor CreA has been described as the major CC repressor in Aspergillus spp., although little is known about the role of posttranslational modifications in this process. In this work, phosphorylation sites were identified by mass spectrometry on Aspergillus nidulans CreA, and subsequently, the previously identified but uncharacterized site S262, the characterized site S319, and the newly identified sites S268 and T308 were chosen to be mutated to nonphosphorylatable residues before their effect on CCR was investigated. Sites S262, S268, and T308 are important for CreA protein accumulation and cellular localization, DNA binding, and repression of enzyme activities. In agreement with a previous study, site S319 was not important for several here-tested phenotypes but is key for CreA degradation and induction of enzyme activities. All sites were shown to be important for glycogen and trehalose metabolism. This study highlights the importance of CreA phosphorylation sites for the regulation of CCR. These sites are interesting targets for biotechnological strain engineering without the need to delete essential genes, which could result in undesired side effects.IMPORTANCE In filamentous fungi, the transcription factor CreA controls carbohydrate metabolism through the regulation of genes encoding enzymes required for the use of alternative carbon sources. In this work, phosphorylation sites were identified on Aspergillus nidulans CreA, and subsequently, the two newly identified sites S268 and T308, the previously identified but uncharacterized site S262, and the previously characterized site S319 were chosen to be mutated to nonphosphorylatable residues before their effect on CCR was characterized. Sites S262, S268, and T308 are important for CreA protein accumulation and cellular localization, DNA binding, and repression of enzyme activities. In agreement with a previous study, site S319 is not important for several here-tested phenotypes but is key for CreA degradation and induction of enzyme activities. This work characterized novel CreA phosphorylation sites under carbon catabolite-repressing conditions and showed that they are crucial for CreA protein turnover, control of carbohydrate utilization, and biotechnologically relevant enzyme production.

Authors: L. J. de Assis, L. P. Silva, O. Bayram, P. Dowling, Olaf Kniemeyer, Thomas Krüger, Axel Brakhage, Y. Chen, L. Dong, K. Tan, K. H. Wong, L. N. A. Ries, G. H. Goldman

Date Published: 5th Jan 2021

Journal: mBio

Unaltered Fungal Burden and Lethality in Human CEACAM1-Transgenic Mice During Candida albicans Dissemination and Systemic Infection.
FungiNet total, A5

Abstract (Expand)

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a receptor for Candida albicans. It is crucial for the immune response of intestinal epithelial cells to this opportunistic … pathogen. Moreover, CEACAM1 is of importance for the mucosal colonization by different bacterial pathogens. We therefore studied the influence of the human CEACAM1 receptor in human CEACAM1-transgenic mice on the C. albicans colonization and infection utilizing a colonization/dissemination and a systemic infection mouse model. Our results showed no alterations in the host response between the transgenic mice and the wild-type littermates to the C. albicans infections. Both mouse strains showed comparable C. albicans colonization and mycobiota, similar fungal burdens in various organs, and a similar survival in the systemic infection model. Interestingly, some of the mice treated with anti-bacterial antibiotics (to prepare them for C. albicans colonization via oral infection) also showed a strong reduction in endogenous fungi instead of the normally observed increase in fungal numbers. This was independent of the expression of human CEACAM1. In the systemic infection model, the human CEACAM1 expression was differentially regulated in the kidneys and livers of Candida-infected transgenic mice. Notably, in the kidneys, a total loss of the largest human CEACAM1 isoform was observed. However, the overwhelming immune response induced in the systemic infection model likely covered any CEACAM1-specific effects in the transgenic animals. In vitro studies using bone marrow-derived neutrophils from both mouse strains also revealed no differences in their reaction to C. albicans. In conclusion, in contrast to bacterial pathogens interacting with CEACAM1 on different mucosal surfaces, the human CEACAM1-transgenic mice did not reveal a role of human CEACAM1 in the in vivo candidiasis models used here. Further studies and different approaches will be needed to reveal a putative role of CEACAM1 in the host response to C. albicans.

Authors: Esther Klaile, M. M. Muller, C. Zubiria-Barrera, S. Brehme, Tilman Klassert, M. Stock, A. Durotin, T. D. Nguyen, S. Feer, B. B. Singer, Peter Zipfel, Sven Rudolphi, Ilse Jacobsen, Hortense Slevogt

Date Published: 19th Dec 2019

Journal: Front Microbiol

Trends in mathematical modeling of host-pathogen interactions.
FungiNet total, B1

Abstract (Expand)

Pathogenic microorganisms entail enormous problems for humans, livestock, and crop plants. A better understanding of the different infection strategies of the pathogens enables us to derive optimal … treatments to mitigate infectious diseases or develop vaccinations preventing the occurrence of infections altogether. In this review, we highlight the current trends in mathematical modeling approaches and related methods used for understanding host-pathogen interactions. Since these interactions can be described on vastly different temporal and spatial scales as well as abstraction levels, a variety of computational and mathematical approaches are presented. Particular emphasis is placed on dynamic optimization, game theory, and spatial modeling, as they are attracting more and more interest in systems biology. Furthermore, these approaches are often combined to illuminate the complexities of the interactions between pathogens and their host. We also discuss the phenomena of molecular mimicry and crypsis as well as the interplay between defense and counter defense. As a conclusion, we provide an overview of method characteristics to assist non-experts in their decision for modeling approaches and interdisciplinary understanding.

Authors: Jan Ewald, Patricia Sieber, R. Garde, S. N. Lang, Stefan Schuster, B. Ibrahim

Date Published: 30th Nov 2019

Journal: Cell Mol Life Sci

Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies.
FungiNet total, FungiNet C - Candida projects, C4 (E)

Abstract (Expand)

Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of … inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. FHR1, but not factor H, FHR2 or FHR3 strongly induces inflammasome NLRP3 in blood-derived human monocytes, which subsequently secrete IL-1beta, TNFalpha, IL-18 and IL-6. FHR1 triggers the phospholipase C-pathway via the G-protein coupled receptor EMR2 independent of complement. Moreover, FHR1 concentrations of AAV patients negatively correlate with glomerular filtration rates and associate with the levels of inflammation and progressive disease. These data highlight an unexpected role for FHR1 during sterile inflammation, may explain why FHR1-deficiency protects against certain diseases, and identifies potential targets for treatment of auto-inflammatory diseases.

Authors: Sarah Irmscher, S. R. Brix, Peter Zipfel, Luke Donald Halder, S. Mutluturk, S. Wulf, E. Girdauskas, H. Reichenspurner, R. A. K. Stahl, Berit Jungnickel, T. Wiech, Peter Zipfel, Christine Skerka

Date Published: 4th Jul 2019

Journal: Nat Commun

C3 - Modulation of neutrophil antifungal activity by intrinsic and extrinsic stimuli
FungiNet total, FungiNet C - Candida projects, C3
No description specified

Creator: Kerstin Hünniger

Contributor: Kerstin Hünniger

On the role of CEACAM receptors during systemic candidiasis
FungiNet total, FungiNet A - Aspergillus projects, A5
No description specified

Creator: Esther Klaile

Contributor: Esther Klaile

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Molecular characterization of Candida albicans mucosal colonization, infection and translocation
FungiNet total

Talk at internal seminar in Jena_21.11.2017

Creators: Toni Förster, Selene Mogavero, Bernhard Hube, Lydia Kasper, Stefanie Allert

Contributor: Toni Förster

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Annual Meeting CRC/TR 124 FungiNet 2018
No description specified

Start Date: 19th Nov 2018

End Date: 20th Nov 2018

Event Website: Not specified

Country:  Germany

City: Bad Staffelstein

Joint Meeting IMIHM XII & CRC/TR 124 2018-06

This year's 12th IMIHM meeting is held for the fifth time as a Joint Meeting together with scientists from the CRC TransRegio 124 (“Pathogenic fungi and their human host: Networks of interaction – FungiNet”). This collaborative Research Centre FungiNet is a network of scientists from Jena and Wuerzburg and is funded by the Deutsche Forschungsgemeinschaft. The Consortium collaborates to better understand complex invasive mycoses by investigating the pathobiology of fungi, the response of the immune
...

Start Date: 26th Jun 2018

End Date: 27th Jun 2018

Event Website: Not specified

Country:  Germany

City: Würzburg

Joint Meeting IMIHM XI & CRC/TR 124 - September 2017

This year‘s 11 th IMIHM meeting is held for the fourth time as a Joint Meeting together with scientists from the CRC TransRegio 124 (“Pathogenic fungi and their human host: Networks of interaction – FungiNet”). This Collaborative Research Centre FungiNet is a network of scientists from Jena and Wuerzburg and is funded by the Deutsche Forschungsgemeinschaft. The Consortium collaborates to better understand complex invasive mycoses by investigating the pathobiology of fungi, the response of the
...

Start Date: 7th Sep 2017

End Date: 8th Sep 2017

Event Website: Not specified

Country:  Germany

City: Würzburg

SFB FungiNet: Review Meeting in Würburg
No description specified

Start Date: 9th Feb 2017

End Date: 10th Feb 2017

Event Website: Not specified

Country:  Germany

City: Würzburg

SFB FungiNet: Interns Seminar in Jena A5 & B1 - 9.9.2014

9. September 2014

A5 und B1

Slevogt / Schuster

Start Date: 9th Sep 2014

End Date: Not specified

Event Website: Not specified

Country:  Germany

City: Jena

34 hidden items
3 hidden items
Af_15min+O2-C4(75min)
FungiNet total, A1

Type: Template_RNA-seq_V1.9

Creators: Jörg Linde, Falk Hillmann, Olaf Kniemeyer

Contributor: Maja Rey

Af_30min-O2-C3
FungiNet total, A1

Type: Template_RNA-seq_V1.9

Creators: Jörg Linde, Falk Hillmann, Olaf Kniemeyer

Contributor: Maja Rey

Af_15min-O2-C2
FungiNet total, A1

Type: Template_RNA-seq_V1.9

Creators: Jörg Linde, Falk Hillmann, Olaf Kniemeyer

Contributor: Maja Rey

Af_0min+O2-C1
FungiNet total, A1

Type: Template_RNA-seq_V1.9

Creators: Jörg Linde, Falk Hillmann, Olaf Kniemeyer

Contributor: Maja Rey

Af_15min+O2-B4(75min)
FungiNet total, A1

Type: Template_RNA-seq_V1.9

Creators: Jörg Linde, Falk Hillmann, Olaf Kniemeyer

Contributor: Maja Rey

128 hidden items
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