Mycobiology

The Korean Society of Mycology (한국균학회)
권호 표지
DOI QR코드

DOI QR Code

Antifungal Susceptibility Tests and the cyp51 Mutant Strains among Clinical Aspergillus fumigatus Isolates from Korean Multicenters

  • Won, Eun Jeong (Department of Laboratory Medicine, Chonnam National University Medical School) ;
  • Joo, Min Young (Department of Laboratory Medicine, Chonnam National University Medical School) ;
  • Lee, Dain (Department of Laboratory Medicine, Chonnam National University Medical School) ;
  • Kim, Mi-Na (Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center) ;
  • Park, Yeon-Joon (Department of Laboratory Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Soo Hyun (Department of Laboratory Medicine, Chonnam National University Medical School) ;
  • Shin, Myung Geun (Department of Laboratory Medicine, Chonnam National University Medical School) ;
  • Shin, Jong Hee (Department of Laboratory Medicine, Chonnam National University Medical School)
  • Received : 2020.02.24
  • Accepted : 2020.03.16
  • Published : 2020.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

Keywords

References

  1. Patterson TF, Thompson GR, 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1-e60. https://doi.org/10.1093/cid/ciw326
  2. Rivero-Menendez O, Alastruey-Izquierdo A, Mellado E, et al. Triazole resistance in Aspergillus spp.: a worldwide problem? J Fungi. 2016;2(3):21. https://doi.org/10.3390/jof2030021
  3. Verweij PE, Snelders E, Kema GH, et al. Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?. Lancet Infect Dis. 2009;9(12):789-795. https://doi.org/10.1016/S1473-3099(09)70265-8
  4. Wiederhold NP, Gil VG, Gutierrez F, et al. First detection of TR34 L98H and TR46 Y121F T289A Cyp51 mutations in Aspergillus fumigatus isolates in the United States. J Clin Microbiol. 2016;54(1):168-171. https://doi.org/10.1128/JCM.02478-15
  5. Escribano P, Recio S, Pelaez T, et al. Aspergillus fumigatus strains with mutations in the cyp51A gene do not always show phenotypic resistance to itraconazole, voriconazole, or posaconazole. Antimicrob Agents Chemother. 2011;55(5):2460-2462. https://doi.org/10.1128/AAC.01358-10
  6. Kidd SE, Goeman E, Meis JF, et al. Multi-triazoleresistant Aspergillus fumigatus infections in Australia. Mycoses. 2015;58(6):350-355. https://doi.org/10.1111/myc.12324
  7. Pham CD, Reiss E, Hagen F, et al. Passive surveillance for azole-resistant Aspergillus fumigatus, United States, 2011-2013. Emerg Infect Dis. 2014;20(9):1498-1503. https://doi.org/10.3201/eid2009.140142
  8. Chen Y, Lu Z, Zhao J, et al. Epidemiology and molecular characterizations of azole resistance in clinical and environmental Aspergillus fumigatus isolates from China. Antimicrob Agents Chemother. 2016;60(10):5878-5884. https://doi.org/10.1128/AAC.01005-16
  9. Lee HJ, Cho SY, Lee DG, et al. TR34/L98H Mutation in CYP51A Gene in Aspergillus fumigatus clinical isolates during posaconazole prophylaxis: first case in Korea. Mycopathologia. 2018;183(4):731-736. https://doi.org/10.1007/s11046-018-0271-8
  10. Heo MS, Shin JH, Choi MJ, et al. Molecular identification and amphotericin B susceptibility testing of clinical isolates of Aspergillus from 11 hospitals in Korea. Ann Lab Med. 2015;35(6):602-610. https://doi.org/10.3343/alm.2015.35.6.602
  11. CLSI. 2008. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. 2nd ed. CLSI document M38-A2. Wayne, PA: Clinical and Laboratory Standards Institute.
  12. Espinel-Ingroff A, Turnidge J. The role of epidemiological cutoff values (ECVs/ECOFFs) in antifungal susceptibility testing and interpretation for uncommon yeasts and moulds. Rev Iberoam Micol. 2016;33(2):63-75. https://doi.org/10.1016/j.riam.2016.04.001
  13. Garcia-Rubio R, Alcazar-Fuoli L, Monteiro MC, et al. Insight into the significance of Aspergillus fumigatus cyp51A polymorphisms. Antimicrob Agents Chemother. 2018;62(6):e00241-18.
  14. van der Linden J, Arendrup M, Warris A, et al. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus. Emerg Infect Dis. 2015;21(6):1041-1044. https://doi.org/10.3201/eid2106.140717
  15. Fraczek MG, Bromley M, Buied A, et al. The cdr1B efflux transporter is associated with noncyp51a-mediated itraconazole resistance in Aspergillus fumigatus. J Antimicrob Chemother. 2013;68(7):1486-1496. https://doi.org/10.1093/jac/dkt075
  16. Rodriguez-Tudela JL, Alcazar-Fuoli L, Mellado E, et al. Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigates. Antimicrob Agents Chemother. 2008;52(7):2468-2472. https://doi.org/10.1128/AAC.00156-08
  17. Snelders E, Karawajczyk A, Schaftenaar G, et al. Azole resistance profile of amino acid changes in Aspergillus fumigatus CYP51A based on protein homology modeling. Antimicrob Agents Chemother. 2010;54(6):2425-2430. https://doi.org/10.1128/AAC.01599-09
  18. Snelders E, Huis In 'T Veld RA, Rijs AJ, et al. Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Appl Environ Microbiol. 2009;75(12):4053-4057. https://doi.org/10.1128/AEM.00231-09
  19. Diaz-Guerra TM, Mellado E, Cuenca-Estrella MA, et al. A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 2003;47(3):1120-1124. https://doi.org/10.1128/AAC.47.3.1120-1124.2003
  20. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813-1821. https://doi.org/10.1086/588660

Cited by

  1. Aspergillus fumigatus and aspergillosis: From basics to clinics vol.100, 2020, https://doi.org/10.1016/j.simyco.2021.100115