Trichophyton rubrum transcriptional profile in response to the host milieu

PERES NT; SILVEIRA HC; GRAS DE; MARANHÃO FC; CAZZANIGA RA; PRADE RA; ROSSI A; MARTINEZ-ROSSI NM

Estambul

Congreso; XII International Congress of Mycology; 2008

Turkish Microbiological Society

Cutaneous mycoses are very common human infections among healthy and immunocompromised hosts, being the anthropophilic fungus Trichophyton rubrum the most prevalent microorganism isolated from these clinical cases worldwide. Although it is a widespread infection, little is known about the pathogenic process in dermatophytosis and the mostly known virulence factors so far are the enzymes released during colonization and maintenance of the fungus in the host tissue, such as keratinases, proteinases and lipases, among others. It has also been reported that the release of these enzymes during the pathogenic process is regulated by the host environmental pH, which is modulated by fungal metabolites as it grows, suggesting that pH sensing and adaptation is a very important step in the infectious process. In order to identify new microbial targets and develop more effective antifungal therapies, it is crucial to understand the cellular and molecular mechanisms of the disease. In this way, the aim of our study is to evaluate some molecular aspects of T. rubrum biology, mainly the factors possibly involved in the infectious process. Moreover, since this dermatophyte is an anthropophilic fungus and there is no murine infection model to analyze host-pathogen interactions, we developed an ex vivo human skin infection system that enabled us to study the genes probably expressed during the infection. We analyzed the genes overexpressed during growth using keratin as nutrient source, acidic or alkaline growth conditions, and during human skin ex vivo infection, using the subtractive suppressive hybridization (SSH) methodology. The analysis of T. rubrum responses during infection, and usage of molecules presented in the host tissue, as well as pH sensing, could reveal the molecular aspects required for the organism to survive in the host milieu. Therefore, the up-regulated genes during skin infection, keratin growth and pH signaling provide insights into metabolic adaptations performed by T. rubrum during host infection, and these findings encourage further studies about pathogenesis, such as the search for new molecular targets for antifungal therapy, as much as new therapeutical approaches.