Changing of the profile of cyp51A mutations of Aspergillus fumigatus clinical strains isolated in Japan

A Watanabe1, D Hagiwara1, 4, T Toyotome2, T Yaguchi3, K Kamei1

Author address: 

1Division of Clinical Research, Medical Mycology Research Center, Chiba University, Japan 2Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan 3Management of Unit of Microbiological Resources, Medical Mycology Research Center, Chiba University, Japan 4 Faculty of Life and Environmental Sciences, University of Tsukuba, Japan


Purpose: Increasing of the rate of azole resistant strains among the clinical isolates of A. fumigatus is becoming a serious concern worldwide. To know the recent status of azole resistance of the fungus in Japan, we investigated antifungal susceptibility and cyp51A mutations of clinical isolates of A. fumigatus in the culture collection of Medical Mycology Research Center, Chiba University (MMRC).

Methods: We tested antifungal susceptibilities according to CLSI M38A2. Regarding azole-resistant strains, we analyzed the cyp51A gene of each resistant strain.

Results: Total of 411 A. fumigatus strains which isolated from patients between 2011 and 2016 were examined. Among these strains, 25 (6.1%) isolates were determined as resistant to azole(s). The tandem repeat in cyp51A promoter region was detected in 3 strains. Sixteen strains had point mutation in cyp51A gene, and isolated from patients with the history of given azole(s). Particularly, all of the strains with G448S mutation were isolated from patients to whom voriconazole had administered. By Fisher’s exact test, the G448S mutation is correlated with the administration of voriconazole in each patient (P=0.0239). The remaining 6 strains had no mutation in cyp51A.

Conclusion: In the previous report (Tashiro M, AAC 2012), only G54 mutation were found in resistant A. fumigatus strains, but changing the profile of cyp51A mutation are emerging in Japan.


Full conference title: 

The 8th Advances Against Aspergillus, Lisbon Conference Center, Lisbon, Portugal
    • AAA 8th (2018)