Functional characterization of genes involved in mechanisms of response and resistance to acriflavine in dermatophytes

Abstract

Cytotoxic agents are commonly used to control infections, but their mechanism of action is often poorly understood. Dermatophytes of the genus Trichophyton infect healthy individuals and dermatophytosis are among the few fungal diseases that are transmitted directly from person to person. T. rubrum is a cosmopolitan fungus and the most common cause of nail and skin infections. It is, in many cases, resistant to treatment, causing allergic reactions and decreases patients quality of life. Despite its importance, little is known about the molecular basis of pathogenesis and gene expression pattern in response to antifungal agents. Large scale transcriptional analysis of T. rubrum in response to acriflavine showed differential modulation of genes possibly associated with the installation and maintenance of infection that may correspond to potential therapeutic targets. This project aims to elucidate the molecular basis of the adaptability of fungi that enable their survival in the host and to identify genes whose products are potential therapeutic targets. Furthermore, these results may reveal regulatory circuits that might be involved in the stress response caused by exposure to antifungal drugs.