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Antimicrobial Agents and Chemotherapy, December 2008, p. 4220-4227, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.01431-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B{triangledown} ,{dagger}

Poonam Gautam,1,{ddagger},§ Jata Shankar,1,{ddagger},¶ Taruna Madan,1* Ravi Sirdeshmukh,2 Curam Sreenivasacharlu Sundaram,2 Wasudev Namdeo Gade,3 Seemi Farhat Basir,4 and Puranam Usha Sarma1,||

Molecular Biochemistry and Diagnostics Division, Institute of Genomics and Integrative Biology, Delhi, India,1 Proteomics Research Facility, Centre for Cellular and Molecular Biology, Hyderabad, India,2 Department of Biotechnology, University of Pune, Pune, India,3 Department of Biosciences, Jamia Millia Islamia, New Delhi, India4

Received 5 November 2007/ Returned for modification 21 December 2007/ Accepted 28 September 2008

Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections, including invasive aspergillosis. It has been our aim to understand the molecular targets of AMB in Aspergillus fumigatus by genomic and proteomic approaches. In transcriptomic analysis, a total of 295 genes were found to be differentially expressed (165 upregulated and 130 downregulated), including many involving the ergosterol pathway, cell stress proteins, cell wall proteins, transport proteins, and hypothetical proteins. Proteomic profiles of A. fumigatus alone or A. fumigatus treated with AMB showed differential expression levels for 85 proteins (76 upregulated and 9 downregulated). Forty-eight of them were identified with high confidence and belonged to the above-mentioned categories. Differential expression levels for Rho-GDP dissociation inhibitor (Rho-GDI), secretory-pathway GDI, clathrin, Sec 31 (a subunit of the exocyst complex), and RAB GTPase Ypt51 in response to an antifungal drug are reported here for the first time and may represent a specific response of A. fumigatus to AMB. The expression of some of these genes was validated by real-time reverse transcription-PCR. The AMB responsive genes/proteins observed to be differentially expressed in A. fumigatus may be further explored for novel drug development.

* Corresponding author. Present address: Innate Immunity, National Institute for Research in Reproductive Health, JM Street, Parel, Mumbai, India. Phone: 91-22-24192017. Fax: 91-22-24139412. E-mail: taruna_m{at}hotmail.com

{triangledown} Published ahead of print on 6 October 2008.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

{ddagger} Both authors contributed equally.

§ Present address: Proteomics Research Facility, Centre for Cellular and Molecular Biology, Hyderabad, India.

Present address: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA.

|| Present address: Department of Plant Pathology, Indian Agricultural Research Institute, Pusa, Delhi, India.

Antimicrobial Agents and Chemotherapy, December 2008, p. 4220-4227, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.01431-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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