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Identification of Fungal Species and Detection of Azole-Resistance Mutations in the Aspergillus fumigatus cyp51A Gene at a South Korean Hospital

Authors
 In Young Jung  ;  Youn Jung Lee  ;  Hyo Sup Shim  ;  Yun Suk Cho  ;  Yu Jin Sohn  ;  Jong Hoon Hyun  ;  Yae Jee Baek  ;  Moo Hyun Kim  ;  Jung Ho Kim  ;  Jin Young Ahn  ;  Su Jin Jeong  ;  Nam Su Ku  ;  Yoon Soo Park  ;  Joon Sup Yeom  ;  Young Keun Kim  ;  Hyo Youl Kim  ;  Jun Yong Choi 
Citation
 YONSEI MEDICAL JOURNAL, Vol.61(8) : 698-704, 2020-08 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2020-08
MeSH
Aged ; Aged, 80 and over ; Aspergillus fumigatus / drug effects ; Aspergillus fumigatus / enzymology* ; Aspergillus fumigatus / genetics* ; Azoles / pharmacology* ; Cytochrome P-450 Enzyme System / genetics* ; Drug Resistance, Fungal / drug effects ; Drug Resistance, Fungal / genetics* ; Female ; Hospitals* ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Mutation / genetics* ; Republic of Korea
Keywords
Aspergillosis ; fungus ; mucormycosis ; polymerase chain reaction ; resistance
Abstract
Purpose: With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital.

Materials and methods: A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006-2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed.

Results: Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use.

Conclusion: Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.
Files in This Item:
T202002928.pdf Download
DOI
10.3349/ymj.2020.61.8.698
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Ku, Nam Su(구남수) ORCID logo https://orcid.org/0000-0002-9717-4327
Kim, Moo Hyun(김무현)
Kim, Jung Ho(김정호) ORCID logo https://orcid.org/0000-0002-5033-3482
Park, Yoon Soo(박윤수)
Baek, Yae Jee(백예지)
Sohn, Yujin(손유진)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Ahn, Jin Young(안진영) ORCID logo https://orcid.org/0000-0002-3740-2826
Yeom, Joon Sup(염준섭) ORCID logo https://orcid.org/0000-0001-8940-7170
Jeong, Su Jin(정수진) ORCID logo https://orcid.org/0000-0003-4025-4542
Jung, In Young(정인영)
Cho, Yunsuk(조윤숙)
Choi, Jun Yong(최준용) ORCID logo https://orcid.org/0000-0002-2775-3315
Hyun, Jong Hoon(현종훈) ORCID logo https://orcid.org/0000-0002-9621-0250
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179657
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