Knocking out the pptA gene in Aspergillus fumigatus could result in new protein profile and promising targets for antifungals
The filamentous fungus Aspergillus fumigatus is the most considerable common opportunistic pathogen. This is due to the prevalence of its occurrence in patients with immune debilities. It can cause diseases with impact extends to life-threatening seriousness. This fungus recently showed interesting means of adaptation, biofilm formation, and morphogenesis within the host biome. Its ability to invade and systematically disperse in the patient’s body is of great concern. The complications of antifungal therapy and the limited target available to treat such infections, urge intensive and thorough research to uncover new more effective targets. The present study revealed a novel possibility of making the pptA an effective address in the fungus for antifungal treatment. Knocking-out the pptA gene resulted in halting pathogenecity as it correlated with essential genes of pathogenecity medA which showed considerable down regulation. Significant increase of protein profile has been discovered in ∆pptA strains as UBC gene highly activated and protein assay revealed high rate of production. In conclusion, the present study emphasize pptA as a possible strong antifungal target and declares high protein output from ∆pptA which may be a promised strain for industrial and beneficial protein production.
Brown, G. D., Denning, D. W., Gow, N. A., Levitz, S. M., Netea, M. G., & White, T. C. (2012). Hidden killers: human fungal infections. Science translational medicine, 4(165), 165rv113-165rv113.
Busby, T. M., Miller, K. Y., & Miller, B. L. (1996). Suppression and enhancement of the Aspergillus nidulans medusa mutation by altered dosage of the bristle and stunted genes. Genetics, 143(1), 155-163.
Chandrasekar, P., Alangaden, G., & Manavathu, E. (2000). Aspergillus: an increasing problem in tertiary care hospitals? Clinical Infectious Diseases, 30(6), 984-985.
Dagenais, T. R., & Keller, N. P. (2009). Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clinical microbiology reviews, 22(3), 447-465.
Denning, D. W., & Bromley, M. J. (2015). How to bolster the antifungal pipeline. Science, 347(6229), 1414-1416.
Denning, D. W., Pleuvry, A., & Cole, D. C. (2011). Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bulletin of the World Health Organization, 89, 864-872.
Denning, D. W., & Hope, W. W. (2010). Therapy for fungal diseases: opportunities and priorities. Trends in microbiology, 18(5), 195-204.
Denning, D. W., Riniotis, K., Dobrashian, R., & Sambatakou, H. (2003). Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clinical infectious diseases, 37(Supplement_3), S265-S280.
Filler, S. G., & Sheppard, D. C. (2006). Fungal invasion of normally non-phagocytic host cells. PLoS pathogens, 2(12), e129.
Fraczek, M. G., Bromley, M., Buied, A., Moore, C. B., Rajendran, R., Rautemaa, R., . . . Bowyer, P. (2013). The cdr1B efflux transporter is associated with non-cyp51a-mediated itraconazole resistance in Aspergillus fumigatus. Journal of Antimicrobial Chemotherapy, 68(7), 1486-1496.
Gupta, R., Chandr, A., & Gautam, P. (2012). Allergic bronchopulmonary aspergillosis--a clinical review. The Journal of the Association of Physicians of India, 60, 46-51.
Haas, H. (2012). Iron–a key nexus in the virulence of Aspergillus fumigatus. Frontiers in microbiology, 3, 28.
Hospenthal, D., Kwon-Chung, K., & Bennett, J. (1998). Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation. Medical mycology, 36(3), 165-168.
Kousha, M., Tadi, R., & Soubani, A. (2011). Pulmonary aspergillosis: a clinical review. European Respiratory Review, 20(121), 156-174.
Ren, S., Zhang, F., Li, C., Jia, C., Li, S., Xi, H., . . . Wang, Y. (2010). Selection of housekeeping genes for use in quantitative reverse transcription PCR assays on the murine cornea. Molecular vision, 16, 1076.
Richie, D. L., Feng, X., Hartl, L., Aimanianda, V., Krishnan, K., Powers-Fletcher, M. V., . . . Willett, T. (2011). The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR). Virulence, 2(1), 12-21.
Schöbel, F., Jacobsen, I. D., & Brock, M. (2010). Evaluation of lysine biosynthesis as an antifungal drug target: biochemical characterization of Aspergillus fumigatus homocitrate synthase and virulence studies. Eukaryotic cell, 9(6), 878-893.
Shankar, J., Madan, T., Basir, S. F., & Sarma, P. U. (2005). Identification and characterization of polyubiquitin gene from cDNA library of Aspergillus fumigatus. Indian Journal of Clinical Biochemistry, 20(1), 208-212.
Szewczyk, E., Nayak, T., Oakley, C. E., Edgerton, H., Xiong, Y., Taheri-Talesh, N., . . . Oakley, B. R. (2006). Fusion PCR and gene targeting in Aspergillus nidulans. Nature protocols, 1(6), 3111.
Twumasi-Boateng, K., Yu, Y., Chen, D., Gravelat, F. N., Nierman, W. C., & Sheppard, D. C. (2009). Transcriptional profiling identifies a role for BrlA in the response to nitrogen depletion and for StuA in the regulation of secondary metabolite clusters in Aspergillus fumigatus. Eukaryotic cell, 8(1), 104-115.
Vos, T., Flaxman, A. D., Naghavi, M., Lozano, R., Michaud, C., Ezzati, M., . . . Aboyans, V. (2012). Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet, 380(9859), 2163-2196.
Walsh, C. T., Gehring, A. M., Weinreb, P. H., Quadri, L. E., & Flugel, R. S. (1997). Post-translational modification of polyketide and nonribosomal peptide synthases. Current opinion in chemical biology, 1(3), 309-315.
Walsh, T., Groll, A., Hiemenz, J., Fleming, R., Roilides, E., & Anaissie, E. (2004). Infections due to emerging and uncommon medically important fungal pathogens. Clinical Microbiology and Infection, 10, 48-66.
Yu, J.-H., Mah, J.-H., & Seo, J.-A. (2006). Growth and developmental control in the model and pathogenic aspergilli. Eukaryotic cell, 5(10), 1577-1584.
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