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Population differentiation, antifungal susceptibility, and host range of Trichophyton mentagrophytes isolates causing recalcitrant infections in humans and animals
European Journal of Clinical Microbiology & Infectious Diseases ( IF 4.5 ) Pub Date : 2020-06-30 , DOI: 10.1007/s10096-020-03952-2
Sebastian Gnat , Dominik Łagowski , Aneta Nowakiewicz , Marcelina Osińska , Łukasz Kopiński

The major problems in determining the causative factors of the high prevalence of dermatophytoses include the lack of a well-standardized antifungal susceptibility testing method, the low consistency of in vitro and clinical minimal inhibitory concentration values, the high genomic diversity of the population, and the unclear mechanism of pathogenicity. These factors are of particular importance when the disease is recalcitrant and relapses. Herein, we identified and characterized Trichophyton mentagrophytes isolates obtained from therapy-resistant cases in humans and animals. We used genomic diversity analysis of 17 human and 27 animal clinical isolates with the MP-PCR technique, determined their phenotypic enzymatic activity and host range, and performed antifungal susceptibility testing to currently available antifungal drugs from various chemical groups. Genomic diversity values of 35.3% and 33.3% were obtained for clinical isolates from humans and animals, respectively, yet without any relationship to the host species or antifungal drug to which resistance in therapy was revealed. The highest activity of keratinase enzymes was recorded for fox, guinea pig, and human hairs. These hosts can be considered as the main species in the host range of these isolates. A phenyl morpholine derivative, i.e. amorolfine, exhibited superior activity against strains obtained from both humans and animals with the lowest MIC50. Interestingly, high compliance of terbinafine in vitro resistance with clinical problems in the treatment with this substance was shown as well. The high resistance of dermatophytes to drugs is the main cause of the recalcitrance of the infection, whereas the other features of the fungus are less important.



中文翻译:

导致人类和动物顽固性感染的毛癣菌分离株的种群分化,抗真菌药性和宿主范围

确定皮肤癣菌高发的病因的主要问题包括缺乏标准化的抗真菌药敏试验方法,体外和临床最小抑菌浓度值一致性低,人群的基因组多样性高以及致病机理尚不清楚。当疾病顽固和复发时,这些因素特别重要。在这里,我们确定和表征毛癣菌从人类和动物的抗药性病例中分离得到的分离株。我们使用MP-PCR技术对17个人类和27个动物临床分离株进行了基因组多样性分析,确定了它们的表型酶活性和宿主范围,并对来自不同化学组的当前可用抗真菌药进行了抗真菌药敏试验。从人和动物的临床分离株分别获得35.3%和33.3%的基因组多样性值,但与治疗中显示出耐药性的宿主物种或抗真菌药物没有任何关系。狐狸,豚鼠和人的头发中角蛋白酶的活性最高。这些寄主被认为是这些分离物寄主范围内的主要物种。苯基吗啉衍生物,即阿莫罗芬,50。有趣的是,也显示了特比萘芬的体外抗药性与该物质治疗中的临床问题高度吻合。皮肤真菌对药物的高耐药性是造成感染顽固的主要原因,而真菌的其他特征则不太重要。

更新日期:2020-06-30
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