The <i>yapA</i> Encodes bZIP Transcription Factor Involved in Stress Tolerance in Pathogenic Fungus <i>Talaromyces marneffei</i>

<div><p><i>Talaromyces marneffei</i>, formerly <i>Penicillium marneffei</i>, is a thermally dimorphic fungus. It causes a fatal disseminated disease in patients infected with the human immunodeficiency virus (HIV). Studies on the stress defense mechanism of <i>T</i>. <i>marneffei</i> can lead to a better understanding of the pathogenicity and the progression of the disease due to this fungus. The basic leucine-zipper (bZip) transcription factor gene in <i>Saccharomyces cerevisiae</i>, named <i>yap1</i> (yeast activating protein-1), is known as a crucial central regulator of stress responses including those caused by oxidative agents, cadmium, and drugs. An ortholog of <i>yap1</i>, designated <i>yapA</i>, was identified in <i>T</i>. <i>marneffei</i>. We found that the <i>yapA</i> gene was involved in growth and fungal cell development. The <i>yapA</i> deletion mutant exhibited delays in the rate of growth, germination, and conidiation. Surprisingly, the <i>yapA</i> gene was also involved in the pigmentation of <i>T</i>. <i>marneffei</i>. Moreover, the mutant was sensitive to oxidative stressors such as H₂O₂ and menadione, similar to <i>S</i>. <i>cerevisiae yap1</i> mutant, as well as the nitrosative stressor NaNO₂. In addition, the <i>yapA</i> mutant demonstrated significantly decreased survival in human macrophage THP-1 compared to wild-type and complemented strains. This study reveals the role of <i>yapA</i> in fungal growth, cell development, stress response, and potential virulence in <i>T</i>. <i>marneffei</i>.</p>