title: In-depth 2-DE reference map of Aspergillus fumigatus and its proteomic profiling on exposure to itraconazole.
abstract: Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins. Further, proteome profiling of A. fumigatus was carried out on exposure to ITC, 0.154 μg/ml, the minimum inhibitory concentration (MIC50). Image analysis showed altered levels of 175 proteins (66 upregulated and 109 downregulated) of A. fumigatus treated with ITC as compared to the untreated control. Peptide mass fingerprinting led to the identification of 54 proteins (12 up-regulated and 42 down-regulated). The differentially expressed proteins include proteins related to cell stress, carbohydrate metabolism and amino acid metabolism. We also observed four proteins, including nucleotide phosphate kinase (NDK), that are reported to interact with calcineurin, a protein involved in regulation of cell morphology and fungal virulence. Comparison of differentially expressed proteins on exposure to ITC with artemisinin (ART), an antimalarial drug with antifungal activity(1), revealed a total of 26 proteins to be common among them suggesting that common proteins and pathways are targeted by these two antifungal agents. The proteins targeted by ITC may serve as important leads for development of new antifungal drugs.
authors: CSIR-Institute of Genomics and Integrative Biology, Delhi, India CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Poonam
authors: P
authors: Gautam
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Dolly
authors: D
authors: Mushahary
authors: CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: Wazid
authors: W
authors: Hassan
authors: CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors: Santosh Kumar
authors: SK
authors: Upadhyay
authors: CSIR-Institute of Genomics and Integrative Biology, Delhi, India National Institute for Research in Reproductive Health, Mumbai, India taruna_m@hotmail.com.
authors: Taruna
authors: T
authors: Madan
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Ravi
authors: R
authors: Sirdeshmukh
authors: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: Curam Sreenivasacharlu
authors: CS
authors: Sundaram
authors: CSIR-Institute of Genomics and Integrative Biology, Delhi, India Department of Plant pathology, Indian Agricultural Research Institute, Delhi, India.
authors: Puranam Usha
authors: PU
authors: Sarma
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D037621:Artemisinins / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000737:chemistry* / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005656:Fungal Proteins / Q000032:analysis*; D020869:Gene Expression Profiling; D006801:Humans; D017964:Itraconazole / Q000378:metabolism*; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D020543:Proteome / Q000032:analysis*; D013312:Stress, Physiological
chemical_list: D000935:Antifungal Agents; D037621:Artemisinins; D005656:Fungal Proteins; D020543:Proteome; D017964:Itraconazole; C031327:artemisinin
keywords: Aspergillus fumigatus; itraconazole; proteomics