Department of Preventive Veterinary, Faculty of Veterinary, Federal University of Pelotas, Pelotas, RS, 96010-900, Brazil.
Postgraduate Program in Pathology, Federal University of Health Sciences of Porto Alegre, Porto Alegre, RS, Brazil.
Braz J Microbiol. 2021 Mar;52(1):73-80. doi: 10.1007/s42770-020-00307-z. Epub 2020 May 31.
The treatment of human and animal sporotrichosis is often performed with antifungal agents; however, the emergence of antifungal-resistant strains of Sporothrix species has been reported. We aimed to discuss the ability of Sporothrix species in developing resistance to the conventional antifungals and mechanisms for this.
Published data on databases (PubMed, Science Direct, Google Scholar) were investigated using a combination of keywords from 2008 to 2019 by the StArt tool.
The minimal inhibitory concentrations values based on the Clinical and Laboratory Standards Institute (CLSI) from eight references were classified according to the epidemiological cutoff values in wild-type or non-wild-type strains. In this way, non-wild-type S. schenckii and, mainly, S. brasiliensis isolates were recognized on itraconazole, amphotericin B, terbinafine, and voriconazole, which are strains that deserve more attention toward antifungal control, with a probable risk of mutation to antifungal resistance. Among the few reviewed studied on antifungal resistance, the melanin production capacity (DHN-melanin, L-DOPA melanin, and pyomelanin), the low genetic diversity due to the abnormal number of chromosomes, and the mutation in cytochrome P450 are some of the factors for developing resistance mechanism.
The emergence of Sporothrix species with in vitro antifungal resistance was evidenced and the possible mechanisms for resistance development may be due to the melanin production capacity, genetic diversity and mutations in cytochrome P450. Further studies should be carried out targeting gene expression for the development of antifungal resistance on Sporothrix species in order to prospect new therapeutic targets for human and veterinary use.
人类和动物孢子丝菌病的治疗通常采用抗真菌药物;然而,已经报道了孢子丝菌属的抗真菌耐药菌株的出现。我们旨在讨论孢子丝菌属发展对常规抗真菌药物的耐药性的能力及其机制。
使用 StArt 工具,结合 2008 年至 2019 年数据库(PubMed、Science Direct、Google Scholar)上发表的数据,通过关键词进行了调查。
根据临床和实验室标准研究所(CLSI)的最低抑菌浓度值,从八个参考值中分类,根据野生型或非野生型菌株的流行病学临界值。通过这种方式,发现非野生型 S. schenckii 以及主要的 S. brasiliensis 分离株对伊曲康唑、两性霉素 B、特比萘芬和伏立康唑具有耐药性,这些菌株值得更关注抗真菌控制,可能存在突变导致抗真菌耐药的风险。在为数不多的 reviewed 抗真菌耐药性研究中,黑色素产生能力(DHN-黑色素、L-DOPA 黑色素和吡咯黑色素)、由于染色体异常导致的低遗传多样性以及细胞色素 P450 的突变是产生耐药机制的一些因素。
体外抗真菌耐药性的孢子丝菌属的出现得到了证实,耐药性发展的可能机制可能是由于黑色素产生能力、遗传多样性和细胞色素 P450 的突变。为了寻找人类和兽医用途的新治疗靶点,应进一步针对孢子丝菌属的基因表达进行抗真菌耐药性的研究。