Transcriptomic and Proteomic Profile of Aspergillus fumigatus on Exposure to Artemisinin
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Artemisinin, an antimalarial drug, and its derivatives are reported to have antifungal activity against some fungi. We report its antifungal activity against Aspergillus fumigatus (A. fumigatus), a pathogenic filamentous fungus responsible for allergic and invasive aspergillosis in humans, and its synergistic effect in combination with itraconazole (ITC), an available antifungal drug. In order to identify its molecular targets, we further analyzed transcript and proteomic profiles of the fungus on exposure to the artemisinin. In transcriptomic analysis, a total of 745 genes were observed to be modulated on exposure to artemisinin, and some of them were confirmed by real-time polymerase chain reaction analysis. Proteomic profiles of A. fumigatus treated with artemisinin showed modulation of 175 proteins (66 upregulated and 109 downregulated) as compared to the control. Peptide mass fingerprinting led to the identification of 85 proteins—29 upregulated and 56 downregulated, 65 of which were unique proteins. Consistent with earlier reports of molecular mechanisms of artemisinin and that of other antifungal drugs, we believe that oxidative phosphorylation pathway (64 kDa mitochondrial NADH dehydrogenase), cell wall-associated proteins and enzymes (conidial hydrophobin B protein, cell wall phiA protein, extracellular thaumatin domain protein, 1,3-beta-glucanosyltransferase Gel2) and genes involved in ergosterol biosynthesis (ERG6 and coproporphyrinogen III oxidase, HEM13) are potential targets of artemisinin for further investigations.
KeywordsAspergillus fumigatus Artemisinin Microarray Proteomics
We are grateful to Council of Scientific and Industrial Research and Department of Science and Technology, Government of India, for the financial support. We are grateful to Pathogen Functional Genomics Resource Center (PFGRC) at J. Craig Venter Institute (JCVI, Rockville, Maryland, USA) for providing A. fumigatus microarray slides. We are also thankful to The Centre for Genomic Application (TCGA) for providing the microarray facility. We acknowledge Dr. D. W. Denning, School of Medicine, University of Manchester, Manchester, UK, for providing the Af293 strain. Dr. Poonam Gautam was recipient of Research Associate Fellowship of Department of Science and Technology, Government of India, and Dr. Santosh Kumar Upadhyay was recipient of Senior Research Fellowship of Council of Scientific and Industrial Research, Government of India.
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