MADS-Box Transcription Factor MadsA Regulates Dimorphic Transition, Conidiation, and Germination of Talaromyces marneffei

Abstract

The opportunistic human pathogen <i>Talaromyces marneffei</i> exhibits a temperature-dependent dimorphic transition, which is closely related with its pathogenicity. This species grows as multinucleate mycelia that produce infectious conidia at 25°C, while undergoes a dimorphic transition to generate uninucleate yeast form cells at 37°C. The mechanisms of phenotype switching are not fully understood. The transcription factor <i>madsA</i> gene is a member of the MADS-box gene family. Previously, it was found that overexpression of <i>madsA</i> gene resulted in mycelial growth instead of yeast form at 37°C. In the current study, the <i>madsA</i> deletion mutant (Δ<i>madsA</i>) and complemented strain (CMA) were constructed by genetic manipulation. We compared the phenotypes, growth, conidiation, conidial germination and susceptibility to stresses (including osmotic and oxidative) of the Δ<i>madsA</i> with the wild-type (WT) and CMA strains. The results showed that the Δ<i>madsA</i> displayed a faster process of the yeast-to-mycelium transition than the WT and CMA. In addition, the deletion of <i>madsA</i> led to a delay in conidia production and conidial germination. The tolerance of Δ<i>madsA</i> conidia to hydrogen peroxide was better than that of the WT and CMA strains. Then, RNA-seq was performed to identify differences in gene expression between the Δ<i>madsA</i> mutant and WT strain during the yeast phase, mycelium phase, yeast-to-mycelium transition and mycelium-to-yeast transition, respectively. Gene ontology functional enrichment analyses indicated that some important processes such as transmembrane transport, oxidation-reduction process, protein catabolic process and response to oxidative stress were affected by the <i>madsA</i> deletion. Together, our results suggest that <i>madsA</i> functions as a global regulator involved in the conidiation and germination, especially in the dimorphic transition of <i>T. marneffei</i>. Its roles in the survival, pathogenicity and transmission of <i>T. marneffei</i> require further investigation.