Publications

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5 Publications visible to you, out of a total of 5

Abstract (Expand)

Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.

Authors: S. Machata, M. M. Muller, R. Lehmann, P. Sieber, G. Panagiotou, A. Carvalho, C. Cunha, K. Lagrou, J. Maertens, H. Slevogt, I. D. Jacobsen

Date Published: 12th Oct 2020

Publication Type: Not specified

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: J. Ewald, P. Sieber, R. Garde, S. N. Lang, S. Schuster, B. Ibrahim

Date Published: 30th Nov 2019

Publication Type: Not specified

Abstract (Expand)

Alternative splicing (AS) is an important regulatory mechanism in eukaryotes but only little is known about its impact in fungi. Human fungal pathogens are of high clinical interest causing recurrent or life-threatening infections. AS can be well-investigated genome-wide and quantitatively with the powerful technology of RNA-Seq. Here, we systematically studied AS in human fungal pathogens based on RNA-Seq data. To do so, we investigated its effect in seven fungi during conditions simulating ex vivo infection processes and during in vitro stress. Genes undergoing AS are species-specific and act independently from differentially expressed genes pointing to an independent mechanism to change abundance and functionality. Candida species stand out with a low number of introns with higher and more varying lengths and more alternative splice sites. Moreover, we identified a functional difference between response to host and other stress conditions: During stress, AS affects more genes and is involved in diverse regulatory functions. In contrast, during response-to-host conditions, genes undergoing AS have membrane functionalities and might be involved in the interaction with the host. We assume that AS plays a crucial regulatory role in pathogenic fungi and is important in both response to host and stress conditions.

Authors: P. Sieber, K. Voigt, P. Kammer, S. Brunke, S. Schuster, J. Linde

Date Published: 19th Oct 2018

Publication Type: Not specified

Abstract (Expand)

The term open reading frame (ORF) is of central importance to gene finding. Surprisingly, at least three definitions are in use. We discuss several molecular biological and bioinformatics aspects, and we recommend using the definition in which an ORF is bounded by stop codons.

Authors: P. Sieber, M. Platzer, S. Schuster

Date Published: 26th Jan 2018

Publication Type: Not specified

Abstract (Expand)

Candida glabrata is the second most common pathogenic Candida species and has emerged as a leading cause of nosocomial fungal infections. Its reduced susceptibility to antifungal drugs and its close relationship to Saccharomyces cerevisiae make it an interesting research focus. Although its genome sequence was published in 2004, little is known about its transcriptional dynamics. Here, we provide a detailed RNA-Seq-based analysis of the transcriptomic landscape of C. glabrata in nutrient-rich media, as well as under nitrosative stress and during pH shift. Using RNA-Seq data together with state-of-the-art gene prediction tools, we refined the annotation of the C. glabrata genome and predicted 49 novel protein-coding genes. Of these novel genes, 14 have homologs in S. cerevisiae and six are shared with other Candida species. We experimentally validated four novel protein-coding genes of which two are differentially regulated during pH shift and interaction with human neutrophils, indicating a potential role in host-pathogen interaction. Furthermore, we identified 58 novel non-protein-coding genes, 38 new introns and condition-specific alternative splicing. Finally, our data suggest different patterns of adaptation to pH shift and nitrosative stress in C. glabrata, Candida albicans and S. cerevisiae and thus further underline a distinct evolution of virulence in yeast.

Authors: , S. Duggan, M. Weber, F. Horn, , D. Hellwig, , , R. Martin, ,

Date Published: 13th Jan 2015

Publication Type: Not specified

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