Article thumbnail
Location of Repository

Systems Biology of Fungal Infection

By Fabian Horn, Thorsten Heinekamp, Olaf Kniemeyer, Johannes Pollmächer, Vito Valiante and Axel A. Brakhage


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

Topics: Microbiology
Publisher: Frontiers Research Foundation
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (2012). 956794. Brodsky,I.E.,andMedzhitov,R.(2009). Targeting of immune signalling networks by bacterial pathogens.
  2. (2008). A study of the Candida albicans cell wall proteome.
  3. (2009). A systems biological approach suggests that transcriptional feedback regulation by dual-specificity phosphatase6shapesextracellularsignalrelated kinase activity in RAStransformedfibroblasts.FEBSJ.276,
  4. and Group,E.S.(2003).Influenceof systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients.
  5. (2012). Application of bioluminescence imaging for in vivo monitoring of fungal infections.
  6. (2004). APSES proteins regulate morphogenesis and metabolism in Candida albicans.
  7. (2005). Bioinformatic methods for integrating whole-genome expression results into cellular networks.
  8. (2005). CandidaDB: a genome database for Candida albicans pathogenomics.
  9. (2008). Characterizing emergent properties of immunological systems with multi-cellular rule-based computational modeling.
  10. (2011). Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi.
  11. (2010). Comprehensive annotation of the transcriptome of the human fungal pathogen Candida albicans using RNA-seq.
  12. (2007). Computational prediction of host-pathogen proteinprotein interactions.
  13. Controlled vocabularies and semantics in systems biology.
  14. (2003). Drug induced proteome changes in Candida albicans: comparison of the effect of beta(1,3) glucan synthase inhibitorsandtwotriazoles,fluconazole and itraconazole.
  15. (2007). Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans.
  16. (2009). Evolution of pathogenicity and sexual reproduction in eightCandida genomes.Nature 459,
  17. (2010). Functional genomic profiling of Aspergillus fumigatus biofilm reveals enhanced production of the mycotoxin gliotoxin.
  18. (2009). Gene ontology and the annotation of pathogen genomes: the case of Candida albicans.
  19. (2004). Genome-wide expression profiling reveals genes associated with amphotericin B and fluconazole resistance in experimentally induced antifungal resistant isolates of Candida albicans.
  20. (2012). Genomewidescale-freenetworkinferencefor Candida albicans.
  21. (2008). Genomic islands in the pathogenic filamentousfungusAspergillusfumigatus.
  22. (2001). Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray.
  23. (2009). Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans.
  24. (2007). Infection-related geneexpressioninCandidaalbicans.
  25. (2007). Integration of transcriptome and proteome data from human-pathogenic fungi by using a data warehouse.
  26. (2010). Integrative analysis of the heat shock response in Aspergillus fumigatus.
  27. (2010). Interaction of phagocytes with filamentous fungi.
  28. (2009). ironacquisition within the host.
  29. (2008). Life history determines genetic structure and evolutionary potential of hostparasite interactions.
  30. (2003). Mass spectrometry-based proteomics.
  31. (2009). Monitoring of systemic candidiasis by 18FFDGPET/CT.Eur .J.Nucl.Med.Mol.
  32. (2011). On the way toward systems biology of Aspergillus fumigatus infection.
  33. (2010). Options and considerations when selecting a quantitative proteomics strategy.
  34. (2009). Pathogenesis of Aspergillus fumigatus in invasive aspergillosis.
  35. (2006). Physicochemical modelling of cell signalling pathways.
  36. (2011). Profiling the Aspergillus fumigatus proteome in response to caspofungin.
  37. (2004). Proteomic analysis of Candida albicans cell walls reveals covalently boundcarbohydrate-activeenzymes and adhesins.
  38. (2010). Secreted Aspergillus fumigatus protease Alp1 degrades human complement proteins C3, C4, and C5.
  39. (2007). Sequence resources at the Candida Genome Database.
  40. (2011). SiTaR: a novel tool for transcription factor binding site prediction.
  41. (2009). Surface hydrophobin prevents immune recognition of airborne fungal spores.
  42. (2005). Systemic fungal infections caused by Aspergillus species: epidemiology, infection process and virulence determinants.
  43. (2012). Systems biology of fungal infection
  44. (2009). Systems-level interactionsbetweeninsulin-EGFnetworks amplify mitogenic signaling.
  45. (2012). The Aspergillus Genome Database (AspGD): recent developments in comprehensive multispecies curation, comparative genomics and community resources.
  46. (2007). The Drosophila systemic immune response:sensingandsignallingduring bacterial and fungal infections.
  47. (2010). The host-infecting fungal transcriptome.
  48. (2008). The landscape of human proteinsinteractingwithvirusesand otherpathogens.PLoSPathog.4,e32. doi:10.1371/journal.ppat.0040032
  49. (1975). The Mathematical Theory of Infectious Diseases and its Application. London: Griffin. Barabási,A.-L.,andOltvai,Z.N.(2004). Networkbiology:understandingthe cell’s functional organization.
  50. (2008). The opportunistic human pathogenic fungus Aspergillusfumigatus evadesthehost complement system.
  51. (2006). Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole.Curr.Genet.50,32–44.
  52. (2010). Tuberculosis research: going forward with a powerful “translational systems biology” approach.
  53. (2010). virulence and host immune response in murine hematogenously disseminated candidiasis.
  54. (2010). Yeast evolutionary genomics.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.