SUB6 Subtilisin is Involved During the Initial Adhesion of Trichophyton benhamiae and T. mentagrophytes onto Reconstructed Human Epidermis

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

The growing incidence of dermatophytoses and the emergence of strains resistant to available antifungal agents raise the need for a better understanding of the virulence mechanisms of dermatophytes to identify new therapeutic targets. The proteases of the subtilisin family have previously been highlighted as potential virulence factors for dermatophytes, in particular the protease SUB6, which was first discovered to be an allergen capable of inducing immediate and delayed hypersensitivity skin reactions. Moreover, SUB6 expression and SUB6 protein production were detected during experimental and natural skin infections with several dermatophyte species. In this study, we specifically investigated the importance of SUB6 during Trichophyton benhamiae and T. mentagrophytes dermatophytosis in a reconstructed human epidermis model by comparing parental strains with genetically engineered ones deleted (ΔSUB6) or complemented for the SUB6-encoding gene. Thereby, a role for SUB6 has been identified in the initial steps of adhesion to the host epidermal surface. However, the ΔSUB6 strains were able to finally invade the reconstructed human epidermis, suggesting that SUB6 is a robust fungal marker of infection but not an essential virulence factor.
SUB6枯草菌素参与了benhami毛藻和T. mentagrophytes在重建的人表皮上的初始粘附
皮肤真菌病的发病率不断上升,并且出现了对现有抗真菌药物具有耐药性的菌株,因此需要更好地了解皮肤真菌的毒力机制,以确定新的治疗靶点。枯草菌素家族的蛋白酶以前被强调为皮肤真菌的潜在毒力因子,特别是蛋白酶SUB6,它首先被发现是一种能够诱导即时和延迟超敏皮肤反应的过敏原。此外,在实验和自然皮肤感染中检测了几种皮肤真菌的SUB6表达和SUB6蛋白的产生。在这项研究中,我们通过将亲本菌株与缺失或补充SUB6编码基因的基因工程菌株(ΔSUB6)进行比较,在重建的人类表皮模型中,专门研究了SUB6在benhami毛癣菌和mentagrophytes皮肤癣菌生长过程中的重要性。因此,在宿主表皮表面粘附的初始步骤中,SUB6的作用已被确定。然而,ΔSUB6菌株最终能够侵入重建的人表皮,这表明SUB6是一种强大的真菌感染标志物,但不是必需的毒力因子。
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