K Weber

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

Are you K Weber?

Claim your profile

Publications (7)20.68 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Candida infections are a permanent threat to immunocompromised individuals such as cancer patients, and Candida glabrata has emerged as a major problem in recent years. Resistance may develop during lengthy antifungal therapies and is often mediated by upregulation of fungal drug efflux pumps. During chemotherapy the yeast cell is also exposed to cytotoxic agents that may affect its drug susceptibility. Four C. glabrata isolates, three susceptible and one resistant to fluconazole (FLU), were incubated with 20 μg/ml of doxorubicin (DOX) for 90 min. In a second experiment, the isolates were cultured with DOX for ten days. Samples were taken on subsequent days to determine the minimal inhibitory concentration (MIC) of FLU and to analyze expression of CgCDR1, CgCDR2, CgSNQ2 and CgPDR1. Samples were also used to assess the petite phenotype. Short-term DOX exposure did not induce efflux pump gene expression, but genes were consistently overexpressed in FLU-susceptible isolates during long-term exposure. An increase in MIC values on day 6 in two of the isolates coincided with the first occurrence of petite mutants in all susceptible isolates. The respiratory deficiency of selected petite mutants was confirmed by culturing mutants on agar containing glycerol as the sole carbon source. FLU MIC values for respiratory-deficient clones were ≥64 μg/ml, and efflux pump gene expression was greatly increased. The resistant isolate did not develop mitochondrial dysfunction. In summary, the cytotoxic agent DOX selects for FLU-resistant respiratory-deficient C. glabrata mutants, which may affect antifungal therapy.
    International journal of medical microbiology: IJMM 06/2012; 302(3):155-61. DOI:10.1016/j.ijmm.2012.04.002 · 3.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of doxorubicin (DOX) on the fluconazole (FLU) susceptibility of C. dubliniensis was investigated. Isolates were exposed to DOX and FLU in a chequerboard assay and resistance gene expressions were analysed after DOX exposure. The susceptibility of the yeast to FLU was decreased in the presence of DOX in the chequerboard assay with FIC indices suggesting an antagonistic effect. Gene expression analyses showed an overexpression of CdCDR2. Hence, DOX was found to have an impact on resistance mechanisms in C. dubliniensis isolates.
    Medical mycology: official publication of the International Society for Human and Animal Mycology 09/2011; 50(4):421-6. DOI:10.3109/13693786.2011.608730 · 2.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Two Candida albicans isolates were collected from a HIV-positive patient with recurrent oropharyngeal candidosis (OPC). One isolate was taken during the first episode of oral candidosis [fluconazole susceptible (FLU-S), minimal inhibitory concentration (MIC) = 0.25 mg l(-1) ] and the second after the patient developed refractory OPC and resistance to fluconazole (FLU-R, MIC = 64 mg l(-1)). Both isolates were clonally identical. Different in vitro studies were carried out to assess putative virulence factors of both isolates. Gene expressions of efflux pumps and CSH1 were determined as well as adherence to human epithelial cells, determination of proteinase secretion and biofilm formation activity. Virulence was studied using a disseminated mouse model. All mice challenged with the FLU-S isolate survived the experiment when FLU was given. However, when FLU was absent, the mortality of the FLU-S isolate was higher than that of the FLU-R isolate with no mice surviving the experiment. In vitro studies showed pronounced growth rates of the FLU-S isolate and a more intense biofilm-building activity compared with the FLU-R isolate. The FLU-R isolate highly up-regulated MDR1 and CSH1. This isolate also adhered stronger to the epithelial cell line. The results showed that FLU-S and FLU-R isolates exhibit different virulence factors, which enable the survival of both isolates in adapted environments.
    Mycoses 05/2011; 54(5):e522-30. DOI:10.1111/j.1439-0507.2010.01970.x · 1.81 Impact Factor
  • Source
    K Weber, B Schulz, M Ruhnke
    [Show abstract] [Hide abstract]
    ABSTRACT: Diseases caused by Candida species are an increasing problem. Candida species are associated with high overall mortality, due to a variety of virulence factors such as the yeast-to-hyphal switch and proteolytic enzymes. The phenomenon of microbial communication known as quorum sensing also seems to play an important role. The main characteristics of the quorum-sensing molecule E,E-farnesol are well known for C. albicans. The present study focused on two questions. One of them concerned the secretion of E,E-farnesol by C. albicans and involved a close examination of the effect of the medium (serum) and the origin of the isolates used. The second one dealt with the activity of E,E-farnesol in non-C. albicans species, such as C. tropicalis and C. parapsilosis, e.g. its impact on biofilm formation and growth. Under serum conditions, C. albicans produced up to 58% more E,E-farnesol at 37 degrees C than at 30 degrees C. The growth of all isolates was reduced and delayed by the administration of E,E-farnesol. Of all Candida species, C. tropicalis isolates were most strongly affected by the addition of E,E-farnesol. Biofilm formation on polystyrene was affected by E,E-farnesol treatment in all non-C. albicans species and C. albicans. E,E-farnesol exerts its main effect by altering the metabolic activity and growth inhibition of treated Candida species. The results obtained indicate that the presence of E,E-farnesol in the environment not only regulates the morphology of the Candida species but also affects its fitness. In this regard, the secretion of E,E-farnesol might provide an advantage for members of the microbial community.
    Yeast 09/2010; 27(9):727-39. DOI:10.1002/yea.1769 · 1.74 Impact Factor
  • K Weber, B Schulz, M Ruhnke
    [Show abstract] [Hide abstract]
    ABSTRACT: Resveratrol is a natural stilbene synthesised by plants. This compound has been shown to inhibit the growth of Candida albicans TIMM 1768 efficiently. Till date, no information is available for other Candida species. The evaluation of the antimicrobial activity of resveratrol was analysed by the inhibition of the growth and metabolism assays. Our data indicate that resveratrol is not effective against Candida albicans and non-C. albicans species (C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei) in vitro. The potential candidacidal activity could not be confirmed.
    Mycoses 09/2009; 54(1):30-3. DOI:10.1111/j.1439-0507.2009.01763.x · 1.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Five methods were compared, using conventional PCR, for the isolation of DNA from Aspergillus fumigatus conidia from 1-3-mL samples of whole blood. A lower detection threshold of Aspergillus conidia was achieved using 3-mL rather than 1-mL samples with three of five methods tested.
    Clinical Microbiology and Infection 07/2009; 15(7):686-8. DOI:10.1111/j.1469-0691.2009.02797.x · 5.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Production of E,E-farnesol (FOH) and biofilm formation were studied under various conditions in 56 strains of eight Candida spp. FOH production differed significantly not only between Candida spp. but within Candida albicans strains as well. FOH concentrations and biofilm formation were the highest for C. albicans.
    Antimicrobial Agents and Chemotherapy 06/2008; 52(5):1859-61. DOI:10.1128/AAC.01646-07 · 4.45 Impact Factor