Abstract
BackgroundThe high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases. Candida albicans is an opportunistic fungal pathogen that is the most common cause of fatal fungal infections in humans and costs $2–4 billion dollars to treat in the US alone.MethodsTo accelerate drug discovery, we screened a library of 1581 existing FDA approved drugs, as well as drugs approved abroad, for inhibitors of C. albicans. The screen was done on YPD yeast growth media as well as on the serum plate assay developed in this study.ResultsWe discovered that fifteen drugs, all which were originally approved for treating various infectious and non-infectious diseases, were able to kill Candida albicans. Additionally, one of those drugs, Octodrine, displays wide-spectrum anti-microbial activity. Compared to other selected anti-Candida drugs, Octodrine was shown to be one of the most effective drugs in killing serum-grown Candida albicans without significantly affecting the survival of host macrophages and skin cells.ConclusionsThis approach is useful for the discovery of economically viable new therapies against infectious diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12941-015-0090-4) contains supplementary material, which is available to authorized users.
Highlights
The high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases
Moderate ability of Fluconazole to kill serum-grown Candida albicans at 37 °C It has been reported that host serum markedly inhibits growth of the human fungal pathogen, Candida albicans [22,23,24]
We investigated whether Fluconazole, the widely used anti-Candida drug, was able to kill C. albicans on solid serum plates
Summary
The high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases. Candida albicans is an opportunistic fungal pathogen that is the most common cause of fatal fungal infections in humans and costs $2–4 billion dollars to treat in the US alone. Candida evades and escapes from the host’s innate immunity, causing irritating and recurrent infections that can range from thrush in immunocompetent colonized hosts, to lifethreatening systemic infections in immunocompromised individuals such as patients with HIV, or those receiving immunesuppressing cancer chemotherapy and corticosteroids. Only 10 to 20% of individuals who develop bloodstream Candida infections are seriously immunocompromised. A large majority of patients develop Candida infections because they have become more susceptible while hospitalized due to the use of broad-spectrum antibiotics, surgery, and intravenous catheters. The cost of treating bloodstream Candida infections is $2– 4 billion per year in the US alone [2]. In the US, annual incidence of systemic candidiasis is approximately 70,000 cases per year, which results in the death rate of about 30 to 40%, even after treatment with antifungal therapy [3]
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