Kano Rui, Aramaki Chizu, Murayama Nobuo, Mori Yuko, Yamagishi Kentaro, Yokoi Shinichi, Kamata Hiroshi
Department of Veterinary Pathobiology, Nihon University College of Bioresource Sciences, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan.
Dermatology Services for Dogs and Cats, 1F TANDEM-HIRANO Bldg. 2-11-14 Hirano, Koto-ku, Tokyo 135-0023, Japan.
Med Mycol. 2020 Feb 1;58(2):197-200. doi: 10.1093/mmy/myz037.
Malassezia pachydermatis, a lipophilic and aerobic yeast, is a causative agent of Malassezia dermatitis, a common skin mycosis in dogs and cats. This fungus is also responsible for zoonotic fungal infections in human neonates. Ravuconazole (RVZ) is an antifungal azole compound and the active metabolite of fosravuconazole, which was approved for use in humans in Japan in 2018. In the present study, in vitro RVZ susceptibility and multi-azole resistance of 13 clinical M. pachydermatis strains was investigated using the modified Clinical and Laboratory Standards Institute M27-A3 test. The minimum inhibitory concentrations (MICs) for the 13 isolates ranged from 0.094 to >32 mg/L for itraconazole (ITZ) and from 0.5 to >32 mg/l for RVZ. Similarly, MICs for ITZ- or RVZ-resistant strains (MICs >32 mg/l) were also >32 mg/l for clotrimazole (CTZ), >32 mg/l for miconazole (MCZ), and 0.25 to >32 mg/L for voriconazole (VRZ). BLAST analysis using the NCBI database showed that ERG11 cDNA of the RVZ-resistant strain encoded Gly at codon 461 and Asp in cytochrome p450 encoded by M. pachydermatis ERG11 mRNA. This work is the first report to describe that an RVZ-resistant M. pachydermatis strain contains ERG11 mutations. The affinity of the protein encoded by ERG11 for RVZ may differ from that of ITZ. Therefore, RVZ has considerable therapeutic potential for treating ITZ-resistant canine Malassezia dermatitis. However, RVZ-resistant strains already exist in canine Malassezia dermatitis in Japan.
厚皮马拉色菌是一种嗜脂性需氧酵母，是犬猫常见皮肤真菌病马拉色菌性皮炎的病原体。这种真菌也是人类新生儿人畜共患真菌感染的病原体。雷夫康唑（RVZ）是一种抗真菌唑类化合物，是伏立康唑的活性代谢产物，于2018年在日本被批准用于人类。在本研究中，使用改良的美国临床和实验室标准协会M27-A3试验，研究了13株临床分离的厚皮马拉色菌菌株对RVZ的体外敏感性和多唑耐药性。13株分离株对伊曲康唑（ITZ）的最低抑菌浓度（MIC）范围为0.094至>32mg/L，对RVZ的最低抑菌浓度范围为0.5至>32mg/L。同样，对ITZ或RVZ耐药菌株（MIC>32mg/L），克霉唑（CTZ）的MIC也>32mg/L，咪康唑（MCZ）的MIC>32mg/L，伏立康唑（VRZ）的MIC为0.25至>32mg/L。使用NCBI数据库进行的BLAST分析表明，RVZ耐药菌株的ERG11 cDNA在密码子461处编码甘氨酸，厚皮马拉色菌ERG11 mRNA编码的细胞色素p450中编码天冬氨酸。这项工作是首次报道耐RVZ的厚皮马拉色菌菌株含有ERG11突变。ERG11编码的蛋白质对RVZ的亲和力可能与对ITZ的亲和力不同。因此，RVZ在治疗耐ITZ的犬马拉色菌性皮炎方面具有相当大的治疗潜力。然而，日本犬马拉色菌性皮炎中已经存在耐RVZ的菌株。
