Comparative gene expression analysis in closely related dermatophytes reveals secondary metabolism as a candidate driver of virulence

Summary

A strain of fungal skin pathogen (Trichophyton benhamiae var. luteum) is spreading rapidly among guinea pigs and people in Europe, but scientists didn’t understand why it was more contagious than closely related strains. Researchers compared gene activity in four related fungal species and found that the epidemic strain produces higher levels of toxic compounds called secondary metabolites. These compounds help the fungus escape the body’s immune system and cause infection more effectively than in less dangerous relatives.

Background

Dermatophytes are widespread fungal skin pathogens affecting 20-25% of the world’s population. Trichophyton benhamiae var. luteum is an emerging zoonotic pathogen responsible for epidemic outbreaks in Europe, particularly among guinea pig owners and their children. Despite sharing common hosts and genetic similarity with less epidemic relatives, the molecular basis for enhanced infectivity of T. benhamiae var. luteum remains incompletely understood.

Objective

To identify candidate virulence-associated genes that explain the enhanced infectivity of T. benhamiae var. luteum compared to closely related, less infective taxa within the Trichophyton benhamiae complex. The study used a comparative approach examining four closely related taxa with differing infectivity levels.

Results

Genes associated with secondary metabolism were consistently upregulated under ex vivo conditions, particularly in T. benhamiae var. luteum. Two biosynthetic gene clusters were identified: cluster A linked to vioxanthin, xanthomegnin, and viomellein synthesis, and cluster B of unknown function. Secreted proteases showed uniform upregulation across taxa under ex vivo conditions, suggesting secondary metabolites rather than proteases may discriminate virulence variation.

Conclusion

Secondary metabolism emerges as a candidate driver of enhanced virulence in T. benhamiae var. luteum. The findings highlight the role of secondary metabolites in dermatophyte pathogenesis and suggest targeting these pathways in future diagnostics and treatments. Improved genome annotation of T. benhamiae is needed to better understand the molecular basis of pathogenesis.
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