Division of Infection Control Sciences, Department of Clinical Pharmacy, School of Pharmacy, Showa University.
Department of Fungal Infection, National Institute of Infectious Diseases.
Med Mycol J. 2022 May 31;63(2):27-35. doi: 10.3314/mmj.21-00024. Epub 2022 Feb 16.
Aspergillus lentulus was first reported in 2005 as a cryptic species of Aspergillus fumigatus, and since then, its resistance to azole drugs and the high mortality rate of infected individuals have emerged as problems. Although it has been reported that P450 14-α sterol demethylase (Cyp51) is involved in azole resistance in A. lentulus, the specific resistance mechanism has not been elucidated. In this study, we successfully introduced the entire A. fumigatus cyp51A gene into the cyp51A locus in A. lentulus using the CRISPR/Cas9 genome-editing system. The A. lentulus strains harboring A. fumigatus cyp51A showed reduced minimum inhibitory concentrations for itraconazole and voriconazole compared with those of the parent strain. This finding suggests that Cyp51A is involved in azole resistance in A. lentulus and may contribute to the elucidation of the mechanism of resistance to azole drugs via Cyp51A and to the development of new antifungal drugs. In addition, our successful application of the CRISPR/Cas9 system to A. lentulus opens the door to examination of other gene functions in this fungus.
青霉 lentulus 于 2005 年首次被报道为烟曲霉的一个隐种，自那时以来，其对唑类药物的耐药性和感染个体的高死亡率已成为问题。尽管已经报道 P450 14-α 甾醇脱甲基酶（Cyp51）参与了 A. lentulus 中的唑类耐药性，但具体的耐药机制尚未阐明。在这项研究中，我们使用 CRISPR/Cas9 基因组编辑系统成功地将整个 A. fumigatus cyp51A 基因导入 A. lentulus 的 cyp51A 基因座。与亲本菌株相比，携带 A. fumigatus cyp51A 的 A. lentulus 菌株对伊曲康唑和伏立康唑的最小抑菌浓度降低。这一发现表明 Cyp51A 参与了 A. lentulus 中的唑类耐药性，可能有助于通过 Cyp51A 阐明唑类药物耐药机制，并开发新的抗真菌药物。此外，我们成功地将 CRISPR/Cas9 系统应用于 A. lentulus，为研究该真菌中的其他基因功能开辟了道路。
