The stress responsive and morphologically regulated <it>hsp90 </it>gene from <it>Paracoccidioides brasiliensis </it>is essential to cell viability

• Main Authors: Fernandes Larissa, Arraes Fabrício BM, Andrade Patrícia A, Dantas Alessandra S, Andrade Rosângela V, Nicola André M, Silva-Pereira Ildinete, Felipe Maria
• Format: Article
• Language: English
• Published: BMC 2008-09-01
• Series: BMC Microbiology
• Online Access: http://www.biomedcentral.com/1471-2180/8/158

<p>Abstract</p> <p>Background</p> <p><it>Paracoccidioides brasiliensis </it>is a dimorphic fungus that causes the most prevalent systemic mycosis in Latin America. The response to heat shock is involved in pathogenesis, as this pathogen switches from mycelium to yeast forms in a temperature dependent fashion that is essential to establish infection. HSP90 is a molecular chaperone that helps in the folding and stabilization of selected polypeptides. HSP90 family members have been shown to present important roles in fungi, especially in the pathogenic species, as an immunodominant antigen and also as a potential antifungal therapeutic target.</p> <p>Results</p> <p>In this work, we decided to further study the <it>Pbhsp90 </it>gene, its expression and role in cell viability because it plays important roles in fungal physiology and pathogenesis. Thus, we have sequenced a <it>Pbhsp90 </it>cDNA and shown that this gene is present on the genome as a single copy. We have also confirmed its preferential expression in the yeast phase and its overexpression during dimorphic transition and oxidative stress. Treatment of the yeast with the specific HSP90 inhibitors geldanamycin and radicicol inhibited growth at 2 and 10 μM, respectively.</p> <p>Conclusion</p> <p>The data confirm that the <it>Pbhsp90 </it>gene encodes a morphologically regulated and stress-responsive protein whose function is essential to cell viability of this pathogen. This work also enforces the potential of HSP90 as a target for antifungal therapies, since the use of HSP90 inhibitors is lethal to the <it>P. brasiliensis </it>yeast cells in a dose-responsive manner.</p>