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Gene expression regulation is essential for fungi to adapt to environmental adversities, such as changes in the extracellular pH, nutrient starvation, ionic strength, and temperature. The adaptive response to ambient pH is well characterized in model fungi such as Aspergillus nidulans, and involves the signal transduction pathway consisting of the products of the pal and pacC genes. In the dermatophyte Trichophyton rubrum, the pacC gene was inactivated and the mutant strain showed a decreased activity of keratinases, indicating that, somehow, this gene is involved in the regulation of the keratonolytic activity of this dermatophyte, and consequently in its virulence and pathogenicity. Moreover, protein glycosylation is an important form of post-translational regulation, playing a role in protein folding and stability of glycoproteins of the secretory pathway, cell wall or membrane. The process of protein glycosylation is influenced by extracellular pH and nutritional source. It has also been reported that this type of post-translational regulation is also influenced by the palB and pacC genes, indicating that these genes have a role in glycosylation of secreted enzymes. The objective of this study was to analyze the influence of the pH and nutritional source in the expression of the genes coding for the N-and O-manosylation enzymes, and their possible modulation by PacC in the dermatophyte T. rubrum. To this end, the transcriptional profile of these genes was analyzed, by Real Time PCR, in the H6 (control) and pacC-1 strains, using glucose, glucose with glycine, or keratin as the carbon source, in several culture times, at pH 5.0 or 8.0. Gene expression analysis showed that when the control strain is grown in keratin at pH 5.0 there is an increased expression of the O-manosyltransferase encoding gene, compared to the cultivation in glucose and glucose with glycine. However, at the same conditions the gene coding for the N-manosyltransferase presented higher levels of expression in the mutant strain in relation to the control strain. At pH 8.0 there is a great similarity between the expression profile of these two genes. The obtained results indicate that pacC gene plays an important role in nutrient sensing at acidic pH by modulating the expression of these transferases in the conditions evaluated. These enzymes can activate proteins that play roles in the hydrolysis of keratin, or even forming cell wall glycoproteins that are essential for the adhesion of the fungus to the host cell, suggesting a role of the manosyltransferases in the infectious process.

Influência do Gene pacC na Regulação de Manosiltransferases no Dermatófito Trichophyton rubrum em Função de Variações Nutricionais e pH Ambiente.