:: Volume 21, Number 2 (2017) ::
Back to browse issues page IBJ 2017, 21(2): 84-93
Identification and Evaluation of Novel Drug Targets against the Human Fungal Pathogen Aspergillus fumigatus with Elaboration on the Possible Role of RNA-Binding Protein
Saeid Malekzadeh, Soroush Sardari, Parisa Azerang, Dorsa Khorasanizadeh, Solmaz Agha Amiri, Mohammad Azizi, Nazanin Mohajerani, Vahid Khalaj
Abstract:  

Bakground: Aspergillus fumigatus is an airborne opportunistic fungal pathogen that can cause fatal infections in immunocompromised patients. Although the current anti-fungal therapies are relatively efficient, some issues such as drug toxicity, drug interactions, and the emergence of drug-resistant fungi have promoted the intense research toward finding the novel drug targets. Methods: In search of new antifungal drug targets, we have used a bioinformatics approach to identify novel drug targets. We compared the whole proteome of this organism with yeast Saccharomyces cerevisiae to come up with 153 specific proteins. Further screening of these proteins revealed 50 potential molecular targets in A. fumigatus. Amongst them, RNA-binding protein (RBP) was selected for further examination. The aspergillus fumigatus RBP (AfuRBP), as a peptidylprolyl isomerase, was evaluated by homology modeling and bioinformatics tools. RBP-deficient mutant strains of A. fumigatus were generated and characterized. Furthermore, the susceptibility of these strains to known peptidylprolyl isomerase inhibitors was assessed. Results: AfuRBP-deficient mutants demonstrated a normal growth phenotype. MIC assay results using inhibitors of peptidylprolyl isomerase confirmed a higher sensitivity of these mutants compared to the wild type. Conclusion: Our bioinformatics approach revealed a number of fungal-specific proteins that may be considered as new targets for drug discovery purposes. Peptidylprolyl isomerase, as a possible drug target, was evaluated against two potential inhibitors and the promising results were investigated mechanistically. Future studies would confirm the impact of such target on the antifungal discovery investigations.

Keywords: Aspergillus fumigatus, RNA-binding protein, Peptidylprolyl isomerase, Juglone, RNA interference
Full-Text [PDF 970 kb]      
Type of Study: Full Length | Subject: Medical Biotechnology
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DOI: 10.18869/acadpub.ibj.21.2.84
PMID: 28000798
PMCID: PMC5274715


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Malekzadeh S, Sardari S, Azerang P, Khorasanizadeh D, Agha Amiri S, Azizi M, et al . Identification and Evaluation of Novel Drug Targets against the Human Fungal Pathogen Aspergillus fumigatus with Elaboration on the Possible Role of RNA-Binding Protein. IBJ. 2017; 21 (2) :84-93
URL: http://ibj.pasteur.ac.ir/article-1-1896-en.html
Back to browse issues page Volume 21, Number 2 (2017)
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