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

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.