AIDS: Combatting drug resistance of Candida albicans

Information

  • Research Project
  • 6594303
  • ApplicationId
    6594303
  • Core Project Number
    R21DE015075
  • Full Project Number
    1R21DE015075-01
  • Serial Number
    15075
  • FOA Number
    RFA-DE-02-07
  • Sub Project Id
  • Project Start Date
    12/1/2002 - 22 years ago
  • Project End Date
    11/30/2004 - 20 years ago
  • Program Officer Name
    NOKTA, MOSTAFA A
  • Budget Start Date
    12/1/2002 - 22 years ago
  • Budget End Date
    11/30/2003 - 21 years ago
  • Fiscal Year
    2003
  • Support Year
    1
  • Suffix
  • Award Notice Date
    -
Organizations

AIDS: Combatting drug resistance of Candida albicans

[unreadable] DESCRIPTION (provided by applicant): Candida albicans is a pathogenic yeast that causes serious fungal infections in the immunocompromised and opponunistic Candida infections can be the first indication of immunosuppression in HIV+ individuals. AIDS patients frequently suffer from oropharyngeal candidiasis (OPC) and require antifungal therapy. In the 1990s there was a dramatic increase in the failure of fluconazole therapy for AIDS patients with OPC due to C. albicans strains developing fluconazole resistance. The most common mechanism responsible for high level fluconazole resistance in these yeast was over-expression of drug efflux pump Cdrl p. Globally, OFC remains a major opponunistic infection in HIVIAIDS, and the widespread use of fluconazole in the third world is likely to maintain pressure on C. albicans to develop resistance. The overall objective of this research is to use a novel strategy to improve the treatment of AIDS patients with oral candidiasis by combating azoleresistance in C. albicans. Specific objectives are to: [unreadable] [unreadable] 1. Employ a novel heterologous functional hyper-expression system to determine the mechanism of pumping by Cdrl p, using both in vitro mutagenized Cdrl p and Cdrl proteins from clinical C. albicans isolates (obtained from AIDS patients) that demonstrate high and low pump activities. [unreadable] [unreadable] 2. Use the heterologous functional hyper-expression of Cdrlp to screen a unique combinatorial Doctapeptide library for peptides that inhibit the pump. [unreadable] [unreadable] This work will validate a novel approach to combating azole-resistance in C. albicana An understanding of drug pumping mechanisms may indicate new ways to circumvent efflux-mediated resistance. This project is expected to identify a lead compound with the potential to sensitize resistant strains to azole antifungals. [unreadable] [unreadable]

IC Name
NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH
  • Activity
    R21
  • Administering IC
    DE
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    133462
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    121
  • Ed Inst. Type
  • Funding ICs
    NIDCR:133462\
  • Funding Mechanism
  • Study Section
    ZDE1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    UNIVERSITY OF OTAGO
  • Organization Department
  • Organization DUNS
  • Organization City
    DUNEDIN
  • Organization State
  • Organization Country
    NEW ZEALAND
  • Organization Zip Code
    9054
  • Organization District
    NEW ZEALAND