@article{RemmeleLutherBalkenholetal.2015, author = {Remmele, Christian W. and Luther, Christian H. and Balkenhol, Johannes and Dandekar, Thomas and M{\"u}ller, Tobias and Dittrich, Marcus T.}, title = {Integrated inference and evaluation of host-fungi interaction networks}, series = {Frontiers in Microbiology}, volume = {6}, journal = {Frontiers in Microbiology}, number = {764}, doi = {10.3389/fmicb.2015.00764}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148278}, year = {2015}, abstract = {Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi human and fungi mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host fungi transcriptome and proteome data.}, language = {en} } @article{BenzJonesYounasetal.2015, author = {Benz, Roland and Jones, Michael D. and Younas, Farhan and Maier, Elke and Modi, Niraj and Mentele, Reinhard and Lottspeich, Friedrich and Kleinekath{\"o}fer, Ulrich and Smit, John}, title = {OmpW of Caulobacter crescentus functions as an outer membrane channel for cations}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0143557}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145114}, pages = {e0143557}, year = {2015}, abstract = {Caulobacter crescentus is an oligotrophic bacterium that lives in dilute organic environments such as soil and freshwater. This bacterium represents an interesting model for cellular differentiation and regulation because daughter cells after division have different forms: one is motile while the other is non-motile and can adhere to surfaces. Interestingly, the known genome of C. crescentus does not contain genes predicted to code for outer membrane porins of the OmpF/C general diffusion type present in enteric bacteria or those coding for specific porins selective for classes of substrates. Instead, genes coding for 67 TonB-dependent outer membrane receptors have been identified, suggesting that active transport of specific nutrients may be the norm. Here, we report that high channel-forming activity was observed with crude outer membrane extracts of C. crescentus in lipid bilayer experiments, indicating that the outer membrane of C. crescentus contained an ion-permeable channel with a single-channel conductance of about 120 pS in 1M KCl. The channel-forming protein with an apparent molecular mass of about 20 kDa was purified to homogeneity. Partial protein sequencing of the protein indicated it was a member of the OmpW family of outer membrane proteins from Gram-negative bacteria. This channel was not observed in reconstitution experiments with crude outer membrane extracts of an OmpW deficient C. crescentus mutant. Biophysical analysis of the C. crescentus OmpW suggested that it has features that are special for general diffusion porins of Gram-negative outer membranes because it was not a wide aqueous channel. Furthermore, OmpW of C. crescentus seems to be different to known OmpW porins and has a preference for ions, in particular cations. A putative model for OmpW of C. crescentus was built on the basis of the known 3D-structures of OmpW of Escherichia coli and OprG of Pseudomonas aeruginosa using homology modeling. A comparison of the two known structures with the model of OmpW of C. crescentus suggested that it has a more hydrophilic interior and possibly a larger diameter.}, language = {en} } @article{IrmerTarazonaSasseetal.2015, author = {Irmer, Henriette and Tarazona, Sonia and Sasse, Christoph and Olbermann, Patrick and Loeffler, J{\"u}rgen and Krappmann, Sven and Conesa, Ana and Braus, Gerhard H.}, title = {RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior}, series = {BMC Genomics}, volume = {16}, journal = {BMC Genomics}, number = {640}, doi = {10.1186/s12864-015-1853-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151390}, year = {2015}, abstract = {Background: Invasive aspergillosis is started after germination of Aspergillus fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. Low fungaemia indicates that fungal elements do not reside in the bloodstream for long. Results: We analyzed whether blood represents a hostile environment to which the physiology of A. fumigatus has to adapt. An in vitro model of A. fumigatus infection was established by incubating mycelium in blood. Our model allowed to discern the changes of the gene expression profile of A. fumigatus at various stages of the infection. The majority of described virulence factors that are connected to pulmonary infections appeared not to be activated during the blood phase. Three active processes were identified that presumably help the fungus to survive the blood environment in an advanced phase of the infection: iron homeostasis, secondary metabolism, and the formation of detoxifying enzymes. Conclusions: We propose that A. fumigatus is hardly able to propagate in blood. After an early stage of sensing the environment, virtually all uptake mechanisms and energy-consuming metabolic pathways are shut-down. The fungus appears to adapt by trans-differentiation into a resting mycelial stage. This might reflect the harsh conditions in blood where A. fumigatus cannot take up sufficient nutrients to establish self-defense mechanisms combined with significant growth.}, language = {en} }