Systems Biology of Fungal Infection

Abstract

Elucidation of pathogenicity mechanisms of the most important human-pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections. A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviors in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions. We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modeling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

A Second Stimulus Required for Enhanced Antifungal Activity of Human Neutrophils in Blood Is Provided by Anaphylatoxin C5a

“…To analyze this situation further, the previously established virtual infection model for the quantification of innate effector mechanisms (5) may be extended from a state-based model to a hybrid agent-based model (37). This would allow for an accurate mathematical description of the whole-blood model by explicitly accounting for mechanism of PMN activation: 1) time-dependent cleavage and diffusion of C5a and 2) morphological changes of C. albicans.…”

Fungal model systems and the elucidation of pathogenicity determinants

“…The main goals are to identify and validate new drugs and new drug targets, increase the efficiency of pathogen identification during an infection and identify effective therapies (Horn et al, 2012). …”

Defining the transcriptomic landscape ofCandida glabrataby RNA-Seq

“…Knowledge about the molecular mechanisms employed by C. glabrata to infect humans remains limited. Although transcriptome studies are helpful to understand infection biology of pathogenic fungi ( 18 ), studies investigating the transcriptome of C. glabrata under relevant conditions are relatively rare ( 19 – 23 ).…”