Filter and export

Publications

What is a Publication?
34 Publications visible to you, out of a total of 34
Regulation of fungal secondary metabolism

Abstract (Expand)

Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular … communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.

Author: Axel A Brakhage

Date Published: 26th Nov 2012

Publication Type: Not specified

Comparison of transcriptome technologies in the pathogenic fungus Aspergillus fumigatus reveals novel insights into the genome and MpkA dependent gene expression

Abstract

ABSTRACT:

Authors: Sebastian Müller, Clara Baldin, Marco Groth, Reinhard Guthke, Olaf Kniemeyer, Axel A Brakhage, Vito Valiante

Date Published: 2nd Oct 2012

Publication Type: Not specified

Regulatory interactions for iron homeostasis in Aspergillus fumigatus inferred by a Systems Biology approach

Abstract (Expand)

BACKGROUND: In System Biology, iterations of wet-lab experiments followed by modelling approaches and model-inspired experiments describe a cyclic workflow. This approach is especially useful for the … inference of gene regulatory networks based on high-throughput gene expression data. Experiments can verify or falsify the predicted interactions allowing further refinement of the network model. Aspergillus fumigatus is a major human fungal pathogen. One important virulence trait is its ability to gain sufficient amounts of iron during infection process. Even though some regulatory interactions are known, we are still far from a complete understanding of the way iron homeostasis is regulated. RESULTS: In this study, we make use of a reverse engineering strategy to infer a regulatory network controlling iron homeostasis in A. fumigatus. The inference approach utilizes the temporal change in expression data after a change from iron depleted to iron replete conditions. The modelling strategy is based on a set of linear differential equations and offers the possibility to integrate known regulatory interactions as prior knowledge. Moreover, it makes use of important selection criteria, such as sparseness and robustness. By compiling a list of known regulatory interactions for iron homeostasis in A. fumigatus and softly integrating them during network inference, we are able to predict new interactions between transcription factors and target genes. The proposed activation of the gene expression of hapX by the transcriptional regulator SrbA constitutes a so far unknown way of regulating iron homeostasis based on the amount of metabolically available iron. This interaction has been verified by Northern blots in a recent experimental study. In order to improve the reliability of the predicted network, the results of this experimental study have been added to the set of prior knowledge. The final network includes three SrbA target genes. Based on motif searching within the regulatory regions of these genes, we identify potential DNA-binding sites for SrbA. Our wet-lab experiments demonstrate high-affinity binding capacity of SrbA to the promoters of hapX, hemA and srbA. CONCLUSIONS: This study presents an application of the typical Systems Biology circle and is based on cooperation between wet-lab experimentalists and in silico modellers. The results underline that using prior knowledge during network inference helps to predict biologically important interactions. Together with the experimental results, we indicate a novel iron homeostasis regulating system sensing the amount of metabolically available iron and identify the binding site of iron-related SrbA target genes. It will be of high interest to study whether these regulatory interactions are also important for close relatives of A. fumigatus and other pathogenic fungi, such as Candida albicans.

Authors: , P. Hortschansky, E. Fazius, , , H. Haas

Date Published: 19th Jan 2012

Publication Type: Not specified

Surface display of Gaussia princeps luciferase allows sensitive fungal pathogen detection during cutaneous aspergillosis

Abstract (Expand)

Non-invasive imaging techniques in microbial disease models have delivered valuable insights in the intimate pathogen-host interplay during infection. Here we describe evaluation and validation of a … transgenic bioluminescence reporter strain of the human-pathogenic mold Aspergillus fumigatus, one of the main fungal pathogens affecting immunocompromised individuals. Expression and surface display of the Gaussia princeps luciferase allowed sensitive and rapid detection of luminescence emitted from this strain after substrate addition, with photon fluxes strongly correlating to the amounts of fungal conidia or germlings. The reporter strain allowed spatio-temporal monitoring of infection in a cutaneous model of aspergillosis, where neutropenic mice maintained the fungal burden while immunocompetent ones were able to clear it entirely. Most importantly, antifungal therapy could be followed in this type of disease model making use of the bioluminescent A. fumigatus strain. In conclusion, combining sensitivity of the Gaussia luciferase with a surface display expression system in the fungal host allows longitudinal infection studies on cutaneous forms of aspergillosis, providing perspective on drug screening approaches at high-throughput.

Authors: Stefanie Donat, Mike Hasenberg, Tina Schäfer, Knut Ohlsen, Matthias Gunzer, Hermann Einsele, Jürgen Löffler, Andreas Beilhack, Sven Krappmann

Date Published: 2012

Publication Type: Not specified

Powered by
 (v.1.14.2)
About INF | About FungiNet | Funding and Programmes | Credits | Imprint
Copyright © 2008 - 2023 The University of Manchester and HITS gGmbH