title: Transcriptomic and proteomic profile of Aspergillus fumigatus on exposure to artemisinin.
abstract: 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.
authors.affiliation: Institute for Genomics and Integrative Biology, Delhi, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Gautam
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Upadhyay
authors.forename: Wazid
authors.initials: W
authors.lastname: Hassan
authors.forename: Taruna
authors.initials: T
authors.lastname: Madan
authors.forename: Ravi
authors.initials: R
authors.lastname: Sirdeshmukh
authors.forename: Curam Sreenivasacharlu
authors.initials: CS
authors.lastname: Sundaram
authors.forename: Wasudev Namdeo
authors.initials: WN
authors.lastname: Gade
authors.forename: Seemi Farhat
authors.initials: SF
authors.lastname: Basir
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.forename: Puranam Usha
authors.initials: PU
authors.lastname: Sarma
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D004693:Glucan Endo-1,3-beta-D-Glucosidase / Q000378:metabolism; D017964:Itraconazole / Q000494:pharmacology; D008780:Methyltransferases / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D020543:Proteome; D013172:Spores, Fungal / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D037621:Artemisinins; D005656:Fungal Proteins; D020543:Proteome; C481003:phiA protein, Aspergillus nidulans; D017964:Itraconazole; C031327:artemisinin; D003304:Coproporphyrinogen Oxidase; D009245:NADH Dehydrogenase; D008780:Methyltransferases; C117939:1,3-beta-glucanosyltransferase; D004693:Glucan Endo-1,3-beta-D-Glucosidase