• Login
    View Item 
    •   Home
    • Department of Chemical Biology (CBIO)
    • publications of the research group compound profiling and screening (COPS)
    • View Item
    •   Home
    • Department of Chemical Biology (CBIO)
    • publications of the research group compound profiling and screening (COPS)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of HZICommunitiesTitleAuthorsIssue DateSubmit DateSubjectsJournalTypesSubject (MeSH)This CollectionTitleAuthorsIssue DateSubmit DateSubjectsJournalTypesSubject (MeSH)

    My Account

    LoginRegister

    Local Links

    About: PolicyHelmholtz-Zentrum für Infektionsforschung HomepageHZI-Library HomepageContact usOpen AccessPublishing ApproachGetting StartedEditing ProfileBrowsing OptionsUsing SearchSubmitting ContentLicenced Journals & access details here

    Statistics

    Display statistics

    Deletion of the HAMP domains from the histidine kinase CaNik1p of Candida albicans or treatment with fungicides activates the MAP kinase Hog1p in S. cerevisiae transformants

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    12866_2013_Article_2079.pdf
    Size:
    570.1Kb
    Format:
    PDF
    Download
    Average rating
     
       votes
    Cast your vote
    You can rate an item by clicking the amount of stars they wish to award to this item. When enough users have cast their vote on this item, the average rating will also be shown.
    Star rating
     
    Your vote was cast
    Thank you for your feedback
    Authors
    El-Mowafy, Mohammed
    Bahgat, Mahmoud M
    Bilitewski, Ursula
    Issue Date
    2013-09-17
    
    Metadata
    Show full item record
    Abstract
    Abstract Background Microorganisms use two-component signal transduction (TCST) systems to regulate the response of the organism to changes of environmental conditions. Such systems are absent from mammalian cells and are thus of interest as drug targets. Fungal TCST systems are usually composed of a hybrid histidine kinase, comprising the histidine kinase (HisKA) domain and a receiver domain, a histidine phosphotransfer protein and a response regulator. Among the 11 groups of fungal histidine kinases, group III histidine kinases are of particular relevance as they are essential for the activity of different groups of fungicides. A characteristic feature is the N-terminal amino acid repeat domain comprising multiple HAMP domains, of which the function is still largely unknown. In Candida albicans, a fungal human pathogen, three histidine kinases were identified, of which CaNik1p is a group III histidine kinase. Heterologous expression of this protein in Sacchromyces cerevisiae conferred susceptibility to different fungicides. Fungicide activity was associated with phosphorylation of the mitogen activated protein kinase Hog1p. Results We have constructed mutated versions of CaNik1p, from which either all HAMP domains were deleted (CaNik1pΔHAMP) or in which the histidine kinase or the receiver domains were not-functional. Expression of CaNIK1ΔHAMP in S. cerevisiae led to severe growth inhibition. Normal growth could be restored by either replacing the phosphate-accepting histidine residue in CaNik1pΔHAMP or by expressing CaNIK1ΔHAMP in S. cerevisiae mutants, in which single genes encoding several components of the HOG pathway were deleted. Expression of proteins with non-functional histidine kinase or receiver domains resulted in complete loss of susceptibility to antifungals, such as fludioxonil. Conditions leading to growth inhibition of transformants also led to phosphorylation of the MAP kinase Hog1p. Conclusion Our results show that functional histidine kinase and receiver domains of CaNik1p were essential for antifungal susceptibility and for activation of the Hog1p. Moreover, for the first time we show that deletion of all HAMP domains from CaNik1p led to activation of Hog1p without an external stimulus. This phenotype was similar to the effects obtained upon treatment with fungicides, as in both cases growth inhibition correlated with Hog1p activation and was dependent on the functionality of the conserved phosphate-accepting histidine residue.
    Citation
    BMC Microbiology. 2013 Sep 17;13(1):209
    URI
    http://dx.doi.org/10.1186/1471-2180-13-209
    http://hdl.handle.net/10033/620784
    Type
    Journal Article
    Collections
    publications of the research group compound profiling and screening (COPS)

    entitlement

     

    DSpace software copyright © 2002-2023  DuraSpace
    Quick Guide | Kontakt | Feedback abschicken
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.