Dr.

Burger-Kentischer, Anke

Filters

3
Reset filters

Settings
Now showing 1 - 3 of 3
  • Publication
    Communication in biofilms between different species: Candida albicans and Pseudomonas aeruginosa
    ( 2010)
    Purschke, F.
    ;
    Burger-Kentischer, A.
    ;
    Rupp, S.
    ;
    Trick, Iris
    ;
    Hirth, Thomas
    Candida albicans, a polymorphic fungus, and Pseudomonas aeruginosa, a Gram-negative bacterium, are two opportunistic pathogens that can cause serious infections in different sites within the human host. Growing in a particular lifestyle called biofilm they are well protected against the human immune system compared to conspecific in planctonic growth. Therefore these organisms are used as model systems for fungal and bacterial biofilm research. Biofilms are structured communities of microorganisms enclosed in a selfproduced polymeric matrix and adherent to an inert or living surface. One of the hallmarks required for the formation of biofilms is the so-called quorum sensing modulated by specific molecules which regulate this developmental process via defined signal cascades. Farnesol is a quorum sensing molecule used by C. albicans which inhibits fungal biofilm formation. It is mediated through a two-component signal transduction histidin kinase Chk1p. In P. aeruginosa N-3-oxo-dodecanoyl-L-homoserine lactone (3OC12HSL) represents a quorum sensing molecule. It acts as a positive regulator via LasR. Both molecules, which contain twelve-carbon backbones, repress C. albicans filamentation without altering its growth rate. To see how the organisms communicate with each other in biofilms a method to quantify the influence of quorum sensing molecules on C. albicans and P. aeruginosa biofilms was used. To visualize the interaction between both organisms mixed biofilms have been studied. Reporter strains have been constructed to analyse the influence of quorum sensing molecules during biofilm formation. Our results indicate that 3OC12HSL has impact on C. albicans biofilm formation and biofilms of P. aeruginosa are manipulated by farnesol.
  • Publication
    Identification of novel antifungal compounds using a HTS activity-selectivity assay
    ( 2010)
    Keller, P.
    ;
    Burger-Kentischer, A.
    ;
    Finkelmeier, D.
    ;
    Kleymann, G.
    ;
    Wiesmüller, K.H.
    ;
    Lemuth, Karin
    ;
    Hiller, E.
    ;
    Rupp, S.
    Fungal infections represent a serious health problem in industrialized countries. Especially immune suppressed patients are highly susceptible to life-threatening infections by opportunistic fungi. In addition transplant therapy and anticancer drugs have provided an opportunity for fungi to cause serious infections. Treatment of fungal infections largely relies on chemotherapy and is limited by the high cost of the most potent antifungals as well as by the reported emerging resistance to some antifungals. To find novel compounds with broad selective antifungal activity we have developed an assay to identify, evaluate and optimize tolerable and potent antimicrobial agents in compound libraries for drug therapy. This assay covers all potential in vitro targets of the pathogen and the host simultaneously. Moreover it constitutes the smallest unit of a natural infection by incubating host cells in the presence of antimicrobial compounds and the pathogen, e.g. Candida species. Host cell survival is determined to asses the efficiency and selectivity of the respective compound. In addition to the minimal inhibitory concentration for the pathogen, this test system provides the tolerability of the active compound by the host cells, expressed as selectivity index. Using this assay about 100 000 compound derived from pre-selected basic chemical structures have been screened. One of the hits identified in the compound library was investigated in more detail by chemical modification of the lead structure and target identification using transcriptional profiling of C. albicans. Tissue models derived from primary cells are used as second test system providing further information about tissue penetration and tolerability of the test compound. Furthermore the most effective compound is currently tested against other Candida and Aspergillus species. Transcriptome analyses of the fungi treated with the novel compounds are in progress to reveal the cellular targets of the new substances and their mode of action.