Chemogenomic profiling predicts antifungal synergies

Abstract Chemotherapies, HIV infections, and treatments to block organ transplant rejection are creating a population of immunocompromised individuals at serious risk of systemic fungal infections. Since single‐agent therapies are susceptible to failure due to either inherent or acquired resistance,...

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Chi tiết về thư mục
Những tác giả chính: Gregor Jansen, Anna Y Lee, Elias Epp, Amélie Fredette, Jamie Surprenant, Doreen Harcus, Michelle Scott, Elaine Tan, Tamiko Nishimura, Malcolm Whiteway, Michael Hallett, David Y Thomas
Định dạng: Bài viết
Ngôn ngữ:English
Được phát hành: Springer Nature 2009-12-01
Loạt:Molecular Systems Biology
Những chủ đề:
Truy cập trực tuyến:https://doi.org/10.1038/msb.2009.95
Miêu tả
Tóm tắt:Abstract Chemotherapies, HIV infections, and treatments to block organ transplant rejection are creating a population of immunocompromised individuals at serious risk of systemic fungal infections. Since single‐agent therapies are susceptible to failure due to either inherent or acquired resistance, alternative therapeutic approaches such as multi‐agent therapies are needed. We have developed a bioinformatics‐driven approach that efficiently predicts compound synergy for such combinatorial therapies. The approach uses chemogenomic profiles in order to identify compound profiles that have a statistically significant degree of similarity to a fluconazole profile. The compounds identified were then experimentally verified to be synergistic with fluconazole and with each other, in both Saccharomyces cerevisiae and the fungal pathogen Candida albicans. Our method is therefore capable of accurately predicting compound synergy to aid the development of combinatorial antifungal therapies.
số ISSN:1744-4292