由印多蒂内毛癣菌（原须癣毛癣菌ITS基因型VIII）引起的抗真菌耐药性皮肤癣菌病在全球的出现：一项涉及14个国家的基因组研究

Global Emergence of Antifungal-Resistant Dermatophytosis Caused by Trichophyton indotineae (Formerly T. mentagrophytes ITS Genotype VIII): A Genomic Investigation Involving 14 Countries.

作者信息

Dos Santos Amanda Ribeiro, Uhrlaß Silke, Nenoff Pietro, Gold Jeremy A W, Bhuiyan Mohammed Saiful Islam, Goturu Srikumar, Gade Lalitha, Bagal Ujwal R, Peterson Joyce G, Wiederhold Nathan P, Lockhart Shawn R, Järv Helle, Hameed Ammar F, Szepietowski Jacek, Vasani Resham, Singal Archana, Parnell Lindsay, Schwem Brian, Chiller Tom, Litvintseva Anastasia P, Chow Nancy A, Verma Shyam B

机构信息

Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Labopart-Medical Laboratories, Roetha OT Moelbis, Germany.

出版信息

Mycoses. 2025 Aug;68(8):e70101. doi: 10.1111/myc.70101.

DOI:10.1111/myc.70101

PMID:40808374

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12393040/

Abstract

BACKGROUND AND OBJECTIVE

Trichophyton indotineae is a globally emerging, frequently antifungal-resistant fungus causing severe dermatophytosis. To inform prevention efforts, we analysed the genomic epidemiology and resistance to terbinafine (first-line oral antifungal) from a collection of multinational T. indotineae isolates collected from patients with clinically suspected dermatophytosis during 2016-2023.

METHODS

We performed whole genome sequencing and phylogenetic tree analysis based on single-nucleotide polymorphisms (SNPs). T. indotineae phylogenetic results were correlated with patient demographic characteristics and isolate terbinafine susceptibility profiles that were determined by antifungal susceptibility testing and squalene epoxidase gene sequencing. Trichophyton mentagrophytes and Trichophyton interdigitale isolates from the USA, and Trichophyton rubrum isolates from three countries were added for contextual analysis.

RESULTS

Among 347 T. indotineae isolates, 227 (65%) were in vitro resistant to terbinafine. Countries represented were India (43%); Germany (21%); Bangladesh (8%); United States (8%); United Arab Emirates (7%); Iraq (5%); Finland (3%); Poland (2%); Austria, Canada, Cambodia, Estonia, Singapore, and Switzerland (each < 1%). Median SNP difference between isolates was 106 SNPs (range: 0-392). Clustering by age, sex, or country was not observed. One subcluster was composed of terbinafine-resistant isolates with a specific squalene epoxidase gene mutation (F397L) and was widely dispersed among 10 countries. Intra-species genomic diversity was greater among 19 T. rubrum isolates (260 SNPs [range: 73-1038]), or among 10 T. mentagrophytes/T. interdigitale isolates from the USA compared with the intra-species diversity of the T. indotineae isolates.

CONCLUSIONS

Our findings corroborate T. indotineae's recent emergence and ongoing international transmission and suggest the rapid spread of a subset of terbinafine-resistant isolates. Continued efforts are necessary to mitigate this pathogen's spread.

摘要

背景与目的

英都藓样毛癣菌是一种在全球范围内新出现的、常具有抗真菌性的真菌，可引起严重的皮肤癣菌病。为指导预防工作，我们分析了2016年至2023年期间从临床疑似皮肤癣菌病患者中收集的多国英都藓样毛癣菌分离株的基因组流行病学及对特比萘芬（一线口服抗真菌药）的耐药性。

方法

我们基于单核苷酸多态性（SNP）进行了全基因组测序和系统发育树分析。英都藓样毛癣菌的系统发育结果与患者人口统计学特征以及通过抗真菌药敏试验和角鲨烯环氧酶基因测序确定的分离株特比萘芬药敏谱相关。添加了来自美国的须癣毛癣菌和指间毛癣菌分离株以及来自三个国家的红色毛癣菌分离株用于背景分析。

结果

在347株英都藓样毛癣菌分离株中，227株（65%）在体外对特比萘芬耐药。涉及的国家有印度（43%）；德国（21%）；孟加拉国（8%）；美国（8%）；阿拉伯联合酋长国（7%）；伊拉克（5%）；芬兰（3%）；波兰（2%）；奥地利、加拿大、柬埔寨、爱沙尼亚、新加坡和瑞士（均<1%）。分离株之间的SNP差异中位数为106个SNP（范围：0 - 392）。未观察到按年龄、性别或国家聚类的情况。一个亚群由具有特定角鲨烯环氧酶基因突变（F397L）的特比萘芬耐药分离株组成，广泛分布于10个国家。与英都藓样毛癣菌分离株的种内基因组多样性相比，19株红色毛癣菌分离株（260个SNP [范围：73 - 1038]）或来自美国的10株须癣毛癣菌/指间毛癣菌分离株的种内基因组多样性更大。