B3 (E)

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Predictive modelling of host-fungal pathogen interactions by reconstruction of gene regulatory networks

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

SEEK ID: https://funginet.hki-jena.de/projects/26

Public web page: http://www.funginet.de/project-b3.html

Organisms: Aspergillus fumigatus, Candida albicans

INF PALs: No PALs for this Project

Project created: 21st Jul 2015

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Showing 5 out of a possible 10 People Advanced People list for this Project with search and filtering

Theresia Conrad : inactive since 2012-01-01

Projects: B3 (E)

Institutions: Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

Andreas Dix : inactive since 2018-06-07

Projects: B3 (E)

Institutions: Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

Peter Großmann

: inactive since 2020-06-01

Projects: FungiNet total, INF, A1, A2, A3, A4 (E), A5, A6, B1, B3 (E), B4, B5, C1, C2, C3, C4 (E), C5, C6 (E), Z1, Z2, FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, FungiNet C - Candida projects, B2

Institutions: Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

https://orcid.org/0000-0001-6106-724X

Expertise: Metabolic networks, Transcriptional Regulation, Bioinformatics, Integrative Data Analysis, Machine Learning, DNA supercoiling

Tools: LaTeX, Matlab, R, Systems biological modelling

Reinhard Guthke : inactive since 2018-06-07

Projects: FungiNet total, FungiNet B - Bioinformatics projects, FungiNet A - Aspergillus projects, B3 (E), FungiNet C - Candida projects, C5

Institutions: Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

Expertise: Integrative Data Analysis, Mathematical Modelling, Gene Regulatory Network Inference

Tools: ODE, Matlab, R

Bioprocess data analysis (data mining) Transcriptomics and proteomics data analysis and modelling Gene Regulatory Network inference (Reverse engineering) Decision making support systems in diagnostics, therapy and biotechnology

Maja Rey

Projects: INF, FungiNet total, A1, A2, FungiNet A - Aspergillus projects, A3, A4 (E), A5, A6, FungiNet C - Candida projects, C1, C2, C3, C4 (E), C5, C6 (E), FungiNet B - Bioinformatics projects, B3 (E)

Institutions: HITS Heidelberger Institut für Theoretische Studien gGmbH

Expertise: Data Management, Data Curation, Biochemistry, Molecular Biology, Microbiology, Phytopathology

Tools: SABIO-RK, Seek

Within the de.NBI project my functions in the de.NBI-SysBio node comprise content curation, requirements elicitation, and community engagement for the users of biochemical reaction kinetics database SABIO-RK as well as of the data management platform SEEK.

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

The yeast Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of life-threatening invasive mycoses in Europe. Despite the increasing incidence of these infections, the current diagnosis is still difficult and often too late, and options for therapies are limited. Moreover, A. fumigatus and C. albicans have developed multiple sophisticated, specific and unique pathogenicity mechanisms. Many of these mechanisms are not well understood. Research on ...

Projects: FungiNet total, FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, FungiNet C - Candida projects, INF, A1, A2, A3, A4 (E), A5, B1, B2, B3 (E), B4, C1, C2, C3, C4 (E), C5, C6 (E), Z2, Z1, B5, A6, A7, A8, C7

Web page: http://www.funginet.de/home.html

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Friedrich Schiller University Jena, Bioinformatics/High Throughput Analysis, Faculty of Mathematics und Computer Science

Country: Germany

City: 07743 Jena

Web page: Not specified

HITS Heidelberger Institut für Theoretische Studien gGmbH

Country: Germany

City: Heidelberg

Web page: https://www.h-its.org

Leibniz-Institute for Natural Product Research and Infection Biology Hans Knöll Institute (HKI)

Country: Germany

City: 07745 Jena

Web page: http://www.hki-jena.de

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Showing 5 out of a possible 9 Publications Advanced Publications list for this Project with search and filtering

Survival Strategies of Pathogenic Candida Species in Human Blood Show Independent and Specific Adaptations.

INF, B3 (E), C1, C3

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Only four species, Candida albicans, C. glabrata, C. parapsilosis, and C. tropicalis, together account for about 90% of all Candida bloodstream infections and are among the most common causes of invasive … fungal infections of humans. However, virulence potential varies among these species, and the phylogenetic tree reveals that their pathogenicity may have emerged several times independently during evolution. We therefore tested these four species in a human whole-blood infection model to determine, via comprehensive dual-species RNA-sequencing analyses, which fungal infection strategies are conserved and which are recent evolutionary developments. The ex vivo infection progressed from initial immune cell interactions to nearly complete killing of all fungal cells. During the course of infection, we characterized important parameters of pathogen-host interactions, such as fungal survival, types of interacting immune cells, and cytokine release. On the transcriptional level, we obtained a predominantly uniform and species-independent human response governed by a strong upregulation of proinflammatory processes, which was downregulated at later time points after most of the fungal cells were killed. In stark contrast, we observed that the different fungal species pursued predominantly individual strategies and showed significantly different global transcriptome patterns. Among other findings, our functional analyses revealed that the fungal species relied on different metabolic pathways and virulence factors to survive the host-imposed stress. These data show that adaptation of Candida species as a response to the host is not a phylogenetic trait, but rather has likely evolved independently as a prerequisite to cause human infections.IMPORTANCE To ensure their survival, pathogens have to adapt immediately to new environments in their hosts, for example, during the transition from the gut to the bloodstream. Here, we investigated the basis of this adaptation in a group of fungal species which are among the most common causes of hospital-acquired infections, the Candida species. On the basis of a human whole-blood infection model, we studied which genes and processes are active over the course of an infection in both the host and four different Candida pathogens. Remarkably, we found that, while the human host response during the early phase of infection is predominantly uniform, the pathogens pursue largely individual strategies and each one regulates genes involved in largely disparate processes in the blood. Our results reveal that C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis all have developed individual strategies for survival in the host. This indicates that their pathogenicity in humans has evolved several times independently and that genes which are central for survival in the host for one species may be irrelevant in another.

Authors: P. Kammer, S. McNamara, T. Wolf, T. Conrad, S. Allert, F. Gerwien, K. Hunniger, O. Kurzai, R. Guthke, B. Hube, J. Linde, S. Brunke

Date Published: 6th Oct 2020

Publication Type: Not specified

PubMed ID: 33024045

Citation: mBio. 2020 Oct 6;11(5). pii: mBio.02435-20. doi: 10.1128/mBio.02435-20.

Created: 11th Feb 2021 at 08:45, Last updated: 17th Jan 2024 at 10:24

Specific and Novel microRNAs Are Regulated as Response to Fungal Infection in Human Dendritic Cells.

INF, A2, B3 (E), C3

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Within the last two decades, the incidence of invasive fungal infections has been significantly increased. They are characterized by high mortality rates and are often caused by Candida albicans and …

Authors: A. Dix, K. Czakai, I. Leonhardt, K. Schaferhoff, M. Bonin, R. Guthke, H. Einsele, O. Kurzai, J. Loffler, J. Linde

Date Published: 11th Mar 2017

Publication Type: Not specified

PubMed ID: 28280489

Citation: Front Microbiol. 2017 Feb 23;8:270. doi: 10.3389/fmicb.2017.00270. eCollection 2017.

Created: 11th Feb 2021 at 09:34, Last updated: 17th Jan 2024 at 10:24

Use of systems biology to decipher host microbial interactions and predict pathological consequences

FungiNet B - Bioinformatics projects, INF, B3 (E)

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In systems biology, researchers aim to understand complex biological systems as a whole, which is often achieved by mathematical modelling and the analyses of high-throughput data. In this review, we …

Authors: , S. Vlaic, ,

Date Published: 27th Apr 2016

Publication Type: Not specified

PubMed ID: 27113568

Citation:

Created: 10th May 2016 at 08:23, Last updated: 17th Jan 2024 at 10:24

Data-based Reconstruction of Gene Regulatory Networks of Fungal Pathogens

FungiNet B - Bioinformatics projects, INF, B3 (E)

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In the emerging field of systems biology of fungal infection, one of the central roles belongs to the modeling of gene regulatory networks (GRNs). Utilizing omics-data, GRNs can be predicted by …

Authors: , S. Gerber, , S. Vlaic, S. Durmus, T. Cakir, F. E. Sevilgen, ,

Date Published: 22nd Apr 2016

Publication Type: Not specified

PubMed ID: 27148247

Citation:

Created: 10th May 2016 at 08:25, Last updated: 17th Jan 2024 at 10:24

Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis

FungiNet A - Aspergillus projects, FungiNet B - Bioinformatics projects, INF, B3 (E)

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Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk …

Authors: , K. Czakai, J. Springer, M. Fliesser, M. Bonin, , A. L. Schmitt, , ,

Date Published: 21st Mar 2016

Publication Type: Not specified

PubMed ID: 27047454

Citation:

Created: 29th Apr 2016 at 11:39, Last updated: 17th Jan 2024 at 10:24

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