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Potential use of Nikkomycin Z as an anti- Sporothrix spp. drug
Medical Mycology ( IF 2.9 ) Pub Date : 2020-07-07 , DOI: 10.1093/mmy/myaa054
Vanice Rodrigues Poester 1 , Lívia Silveira Munhoz 1 , David Larwood 2, 3 , Marife Martinez 3 , David A Stevens 3, 4 , Melissa Orzechowski Xavier 1, 3
Affiliation  

Sporotrichosis, the most common subcutaneous mycosis in several countries, is caused by the dimorphic fungus, Sporothrix spp. Given some limitations in the treatment of this disease, and the high potential of nikkomycin Z (NikZ) as an antifungal against dimorphic fungi, this study aimed to evaluate the in vitro susceptibility of Sporothrix spp. to NikZ alone and with the drug of choice, itraconazole (ITZ). Seventeen clinical isolates of three Sporothrix spp. species (10 S. brasiliensis, six S. schenckii sensu stricto and one S. globosa) were tested in microdilution and checkerboard assays. Minimal inhibitory concentration (MIC), minimal fungicidal concentration (MFC), fractional inhibitory and fungicidal concentration indexes (FICi and FFCi) were analyzed. MIC of NikZ alone could be determined against S. globosa (12.5 μg/ml) and against 67% (4/6) and 30% (3/10) of the S. schenckii sensu stricto and S. brasiliensis isolates, respectively (≤ 400 μg/ml). Synergism with ITZ was showed against almost all the isolates tested (94%; 16/17), including reversing resistance to ITZ alone in some isolates. Our study shows the potential of NikZ in sporotrichosis treatment. Further studies in experimental models are needed to understand the possible future application of this drug as an alternative therapy or as an adjuvant in sporotrichosis treatment.

中文翻译:

Nikkomycin Z 作为抗孢子丝菌属的潜在用途。药品

孢子丝菌病是几个国家最常见的皮下真菌病,由二形真菌孢子丝菌引起。鉴于在治疗这种疾病方面存在一些局限性,以及尼可霉素 Z (NikZ) 作为抗二形真菌的抗真菌剂的巨大潜力,本研究旨在评估孢子丝菌属的体外易感性。单独使用 NikZ 并与选择的药物伊曲康唑 (ITZ) 一起使用。三种孢子丝菌属的十七个临床分离株。种(10 S. brasiliensis,6 S. schenckii sensu stricto和 1 S. globosa) 在微量稀释和棋盘试验中进行了测试。分析了最小抑菌浓度(MIC)、最小杀真菌浓度(MFC)、分数抑菌和杀真菌浓度指数(FICi和FFCi)。NikZ 单独对S. globosa (12.5 μg/ml) 和 67% (4/6) 和 30% (3/10) 的S. schenckii sensu strictoS. brasiliensis 的 MIC分离株,分别(≤ 400 μg/ml)。与 ITZ 的协同作用对几乎所有测试的分离株都显示出 (94%; 16/17),包括在某些分离株中逆转对 ITZ 的抗性。我们的研究显示了 NikZ 在孢子丝菌病治疗中的潜力。需要对实验模型进行进一步研究,以了解该药物未来可能作为替代疗法或作为孢子丝菌病治疗的佐剂的应用。
更新日期:2020-07-07
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