Trichophyton rubrum transcription profile during ex vivo human skin infection

PERES NT; GRAS DE; FALCÃO JP; ROCHA LB; ROSSI MA; MAZUCATO M; ROSSI A; PRADE RA; MARTINEZ-ROSSI NM

Salvador - Bahia

Congreso; 54º Congresso Brasileiro de Genética; 2008

Sociedade Brasileira de Genética

Host-pathogen interactions involve specific adaptations that allow the pathogen to adhere and penetrate the target tissue, remodel metabolic pathways to scavenge nutrients and adapt to the stress caused by host defense mechanisms. The determination of these metabolic adaptations as well as morphogenesis and stress response interconnection are essential to understand the pathogenic process, and enable the establishment of new therapeutic measures. The use of genomic resources, in particular transcription analysis, generates global gene expression profiles during infection, which may lead to the discovery and characterization of pathogen traits with key roles in adaptation to host environment. Due to the high prevalence of clinical cases of cutaneous infections caused by the anthropophylic fungus Trichophyton rubrum, and the lack of knowledge about the infection process of dermatophytosis, the aim of this work was to evaluate the molecular aspects required for this fungus to survive in the host milieu. To achieve this, an ex vivo human skin infection was used, followed by suppression subtractive hybridization (SSH) methodology, to identify T. rubrum expressed genes during fungal-host interaction. After 96 hours of ex vivo infection, conidial germination and hyphal penetration was observed with scan electron microscopy. SSH and differential screening were performed generating 116 unique Expressed Sequence Tags (ESTs), after CAP3 clustering. EST annotation with protein and T. rubrum EST database revealed 25 novel genes and 13 hypothetical proteins, which expression may be regulated during host interaction, and are somehow involved in T. rubrum-skin interaction/adaptation. Functional categorization by Eukaryotic Ortholog Group (KOG) revealed that 16% of the ESTs are involved in translation, ribosomal structure and biogenesis, 15% in posttranslational modification, protein turnover and chaperones, and 31% were annotated as having a general functional prediction only. In conclusion, we identified 116 T. rubrum up-regulated genes during skin infection, revealing 25 novel genes, which provide insights into the metabolic adaptations performed by T. rubrum during host infection. Furthermore, these results encourage further studies about pathogenesis of dermatophytosis, and the search for new molecular targets for antifungal therapy, as much as new therapeutic approaches.