1
Department of Medical Mycology and Parasitology, School of Medicine, Iran University of Medical Sciences, Tehran, IR Iran
2
Department of Mycology, Faculty of Medical Science, Tarbiat Modares University, Tehran, IR Iran
3
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, IR Iran
Abstract
Background: Aspergillosis is an opportunistic infection caused by Aspergillus spp in immunocompromised patients. The role of HSP90 in Aspergillus drug resistance is still unknown. The aim of this study was to evaluate the correlation between the presence of HSP90 gene and polyene resistance in Aspergillus spp using PCR. Materials and Methods: In this study, 32 Aspergillus strains were used, which were isolated from patients susceptible to aspergillosis through Bronchoalveolar lavage (BAL) and identified by conventional methods. The isolates were cultured on Sabouraud dextrose agar (SDA). Susceptibility testing against amphotericin B was conducted according CLSI standards (M38-A). Also, the presence of HSP90 gene was evaluated using PCR. Results: Of 32 Aspergillus strains used in this study, 16 (50%) isolates were identified as A. Flavus, 12 (37.5%) isolates as A.fumigatus, and 4 (12.5%) isolates as A. terreus. Among these species, 19 (59.37%) isolates were sensitive to amphotericin B whereas 13 (40.62%) were resistant. Moreover, there was a significant difference between the presence of HSP90 gene and resistance to amphotericin B in Aspergillus species.
Conclusions: The presence of HSP90 gene provides evidence that shows this gene may play important role in resistance to amphotericin B in Aspergillus isolates. Although numerous regulatory genes are involved in resistance mechanisms, they remaines to be more clarified
Wingard JR, Ribaud P, Schlamm HT, Herbrecht R. Changes in causes of death over time after treatment for invasive aspergillosis. Cancer.2008; 112(10): 2309-12 .
Smith N , Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J.2011; 37(4):865-72.
Denning DW , Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis complicating sarcoidosis. Eur Respir J.2013; 41(3):621-6.
Kanafani ZA, Perfect JR. Resistance to antifungal agents: Mechanisms and clinical impact. Clin Infect Dis. 2008; 46(1):120-8.
Perlin DS. Antifungal drug resistance: Do molecular methods provide a way forward?," Curr Opin Infect Dis. 2009; 22(6):568-73.
Pasqualotto A, Denning DW. New and emerging treatments for fungal infections. J Antimicrob Chemother. 2008; 61(suppl 1): i19-30.
Groll AH , Tragiannidis A. Recent advances in antifungal prevention and treatment. Semin Hematol. 2009; 46(3):212-29.
Chakrabarti A. Drug resistance in fungi-an emerging problem. Region Health Forum. 2011; 15(1):97-103.
Robbins N, Uppuluri P, Nett J, Rajendran R, Ramage G, Lopez-Ribot JL. Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathog. 2011; 7(9):e1002257.
Fortwendel JR, Juvvadi PR, Pinchai N, Perfect BZ, Alspaugh JA, Perfect JR. Differential effects of inhibiting chitin and 1, 3-β-D-glucan synthesis in ras and calcineurin mutants of Aspergillus fumigatus. Antimicrob Agents chemother. 2009; 53 (2):476-82.
Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, Steinbach WJ. Transcriptional regulation of chitin synthases by calcineurin controls paradoxical growth of Aspergillus fumigatus in response to caspofungin. Antimicrob Agents Chemother. 2010; 54(4):1555-63.
Wiederhold NP, Kontoyiannis DP, Chi J, Prince RA, Tam VH, Lewis RE. Pharmacodynamics of caspofungin in a murine model of invasive pulmonary aspergillosis: Evidence of concentration-dependent activity. J Infect Dis. 2004; 190(8):1464-71.
Wiederhold NP. Attenuation of echinocandin activity at elevated concentrations: A review of the paradoxical effect. Curr Opin Infects Dis. 2007; 20(6):574-8.
Moore C, Sayers N, Mosquera J, Slaven J, Denning DW. Antifungal drug resistance in Aspergillus. J Infect. 2000; 41(3):203-20.
Gomez-Lopez A, Garcia-Effron G, Mellado E, Monzon A, Rodriguez-Tudela JL, Cuenca-Estrella M. In vitro activities of three licensed antifungal agents against Spanish clinical isolates of Aspergillus spp. Antimicrob Agents Chemother. 2003; 47(10):3085-8.
Biamonte MA, Van de Water R,. Arndt JW, Scannevin RH, Perret D, Lee WC. Heat shock protein 90: Inhibitors in clinical trials. J Med Chem. 2010; 53(1):3-17.
LaFayette SL, Collins C, Zaas AK, Schell WA, Betancourt-Quiroz M, Gunatilaka AL. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathog. 2010; 6(8):e1001069.
Pallavi R, Roy N, Nageshan RK, Talukdar P, Pavithra SR, Reddy R. Heat shock protein 90 as a drug target against protozoan infections biochemical characterization of Hsp90 from Plasmodium falciparum and trypanosoma evansi and evaluation of its inhibitor as a candidate drug. J Biol Chem. 2010; 285(49): 37964-75.
Wayne PA. Reference method for broth dilution antifungal susceptibility testing; Approved standard. National committee for clinical laboratory standards, 2002.
Rath P. Susceptibility of Aspergillus strains from culture collections to amphotericin B and itraconazole. J Antimicrob Chem.1998; 41(5):567-70.
Alborzi A, Moeini M, Haddadi P. Antifungal susceptibility of the Aspergillus species by Etest and CLSI reference methods. Arch Iranian Med. 2012; 15(7):429.
Cowen LE , Lindquist S. Hsp90 potentiates the rapid evolution of new traits: Drug resistance in diverse fungi. Science. 2005; 309(5744): 2185-9.
Blum G, Kainzner B, Grif K, Dietrich H, Zelger B, Sonnweber T. In vitro and in vivo role of heat shock protein 90 in amphotericin B resistance of Aspergillus terreus. Clin Microbiol Infect. 2013; 19(1):50-5.
Snelders E, Rijs AJ, Kema GH, Melchers WJ, Verweij PE. Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Appl Environ Microbiol.2009; 75(12): 4053-7.
Walsh TJ, Petraitis V, Petraitiene R, Field-Ridley A, Sutton D, Ghannoum M. Experimental pulmonary aspergillosis due to Aspergillus terreus: Pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J Infect Dis. 2003; 188(2):305-19.
Lass-Flörl C, Cuenca-Estrella M, Denning DW, Rodriguez-Tudela J. Antifungal susceptibility testing in Aspergillus spp. according to EUCAST methodology. Med Mycol. 2006; 44(suppl 1):S319-25.
Perlin DS, Shor E, Zhao Y. Update on antifungal drug resistance. Curr Clin Microbiol Rep. 2015;2(2):84-95.
Shapiro RS, Robbins N, Cowen LE. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev. 2011; 75(2): 213-67.
Ghods,N. , Falahati,M. , Roudbary,M. , Mardani,S. and Seif,F. (2017). Presence of HSP90 Gene in Amphotericin B Resistant Aspergillus Species Isolated from Iranian Immunocompromised Patients. Infection Epidemiology and Microbiology, 3(3), 86-89.
MLA
Ghods,N. , Falahati,M. , Roudbary,M. , Mardani,S. , and Seif,F. . "Presence of HSP90 Gene in Amphotericin B Resistant Aspergillus Species Isolated from Iranian Immunocompromised Patients", Infection Epidemiology and Microbiology, 3, 3, 2017, 86-89.
HARVARD
Ghods,N.,Falahati,M.,Roudbary,M.,Mardani,S.,Seif,F. (2017). 'Presence of HSP90 Gene in Amphotericin B Resistant Aspergillus Species Isolated from Iranian Immunocompromised Patients', Infection Epidemiology and Microbiology, 3(3), pp. 86-89.
CHICAGO
N. Ghods, M. Falahati, M. Roudbary, S. Mardani and F. Seif, "Presence of HSP90 Gene in Amphotericin B Resistant Aspergillus Species Isolated from Iranian Immunocompromised Patients," Infection Epidemiology and Microbiology, 3 3 (2017): 86-89,
VANCOUVER
Ghods,N.,Falahati,M.,Roudbary,M.,Mardani,S.,Seif,F. Presence of HSP90 Gene in Amphotericin B Resistant Aspergillus Species Isolated from Iranian Immunocompromised Patients. Infection Epidemiology and Microbiology, 2017; 3(3): 86-89.