Subtilisin 6 From the Dermatophyte Trichophyton benhamiae Is a Marker of Infection but Not a Unique Virulence Factor.

IF 4.1 2区医学 Q1 DERMATOLOGY Mycoses Pub Date : 2025-02-01 DOI:10.1111/myc.70037

Wilfried Poirier, Émilie Faway, Tsuyoshi Yamada, Kiyotaka Ozawa, Françoise Maréchal, Michel Monod, Yves Poumay, Bernard Mignon

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Abstract

Background: Trichophyton benhamiae is a common dermatophyte whose natural host is the guinea pig and which causes highly inflammatory skin lesions in humans. The subtilisin 6 (SUB6) of this fungus belongs to a family of 12 SUB genes. Its encoding gene, overexpressed in vivo but not in vitro, has been considered a potentially important virulence factor, but its role in pathogenesis remains to be elucidated.

Objectives: The aim of this study was to assess the role of T. benhamiae SUB6 in virulence in a mouse skin infection model.

Methods: To assess the contribution of SUB6 to virulence, SUB6-deleted (ΔSUB6) and complemented strains were generated by genetic transformation. The pathogenicity of these strains was compared with that of the parental strain in vivo in mice, based on the evolution of skin symptoms, histopathological lesions and molecular analyses targeting the expression of host pro-inflammatory genes and fungal genes encoding subtilisins from the same family as SUB6.

Results: The ΔSUB6 strain induced superficial skin signs and histopathological inflammatory lesions similar to those caused by the parental strain. Significant overexpression of the SUB1, SUB3, SUB8 and SUB10 genes in the tissues was observed regardless of the strain tested, with no difference between these strains, reflecting the absence of any compensatory mechanism among subtilisins.

Conclusions: SUB6 appears to be more of a marker of fungal infection than a virulence factor, at least acting alone.

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背景：本哈姆毛癣菌是一种常见的皮肤真菌，其自然宿主是豚鼠，会导致人类皮肤出现高度炎症性病变。这种真菌的枯草蛋白 6（SUB6）属于 12 个 SUB 基因家族。其编码基因在体内过表达，但在体外不表达，被认为是一种潜在的重要毒力因子，但其在致病过程中的作用仍有待阐明：本研究的目的是在小鼠皮肤感染模型中评估 T. benhamiae SUB6 在毒力中的作用：方法：为了评估 SUB6 对毒力的贡献，通过基因转化产生了 SUB6 缺失株（ΔSUB6）和互补株。根据皮肤症状的演变、组织病理学病变以及针对宿主促炎基因和编码与 SUB6 同源的枯草蛋白的真菌基因表达的分子分析，比较了这些菌株与亲本菌株在小鼠体内的致病性：结果：ΔSUB6菌株引起的表皮症状和组织病理学炎症病变与亲本菌株相似。结果：ΔSUB6菌株诱导的浅表皮肤症状和组织病理炎症病变与亲本菌株诱导的症状和组织病理炎症病变相似。无论测试的是哪种菌株，组织中都观察到SUB1、SUB3、SUB8和SUB10基因的显著过表达，这些菌株之间没有差异，这反映出枯草杆菌素之间不存在任何补偿机制：结论：SUB6 似乎是真菌感染的标志物，而不是毒力因子，至少是单独起作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mycoses 医学-皮肤病学

CiteScore

10.00

自引率

8.20%

发文量

143

审稿时长

6-12 weeks

期刊介绍： The journal Mycoses provides an international forum for original papers in English on the pathogenesis, diagnosis, therapy, prophylaxis, and epidemiology of fungal infectious diseases in humans as well as on the biology of pathogenic fungi. Medical mycology as part of medical microbiology is advancing rapidly. Effective therapeutic strategies are already available in chemotherapy and are being further developed. Their application requires reliable laboratory diagnostic techniques, which, in turn, result from mycological basic research. Opportunistic mycoses vary greatly in their clinical and pathological symptoms, because the underlying disease of a patient at risk decisively determines their symptomatology and progress. The journal Mycoses is therefore of interest to scientists in fundamental mycological research, mycological laboratory diagnosticians and clinicians interested in fungal infections.