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

Qiangyi Wang,Liming Xiao,Ence Yang,Tong Li,Minghao Du,Linqi Wang,Linxia Liu,Hui Zhuang,Shuai Wang

doi:10.3389/fmicb.2018.01781

Abstract

The opportunistic human pathogen Talaromyces marneffei 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 madsA gene is a member of the MADS-box gene family. Previously, it was found that overexpression of madsA gene resulted in mycelial growth instead of yeast form at 37°C. In the current study, the madsA deletion mutant (ΔmadsA) 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 ΔmadsA with the wild-type (WT) and CMA strains. The results showed that the ΔmadsA displayed a faster process of the yeast-to-mycelium transition than the WT and CMA. In addition, the deletion of madsA led to a delay in conidia production and conidial germination. The tolerance of ΔmadsA 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 ΔmadsA 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 madsA deletion. Together, our results suggest that madsA functions as a global regulator involved in the conidiation and germination, especially in the dimorphic transition of T. marneffei. Its roles in the survival, pathogenicity and transmission of T. marneffei require further investigation.

Highlights

Talaromyces marneffei is a significant emerging pathogenic fungus endemic in Southeast Asia and South China (Vanittanakom et al, 2006; Hu et al, 2013; Yilmaz et al, 2014)
To better understand the roles of madsA in T. marneffei, its deletion mutant madsA was obtained by homologous recombination in this study
T. marneffei exhibits two distinct mycelium-yeast morphogenetic transitions and secretes the diffusible red pigment only at the mycelical phase, which could be used as a hallmark to indicate the transitions

Summary

Introduction

Talaromyces marneffei (formerly Penicillium marneffei) is a significant emerging pathogenic fungus endemic in Southeast Asia and South China (Vanittanakom et al, 2006; Hu et al, 2013; Yilmaz et al, 2014). Penicilliosis marneffei, the disease caused by T. marneffei, has been the third most prevalent opportunistic infection in HIV-positive patients after tuberculosis and cryptococcosis, and has become an important acquired immune deficiency syndrome defining condition (Supparatpinyo et al, 1994). T. marneffei is capable of alternating between a filamentous and a yeast growth form, a process known as dimorphic transition. Yeast cells are found in infected patients, suggesting that they are the pathogenic form (Boyce and Andrianopoulos, 2013). The morphogenetic transition is critical for both pathogenicity and transmission of T. marneffei (Boyce and Andrianopoulos, 2015). T. marneffei is categorized as thermally dimorphic fungi, along with Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, and Sporothrix schenckii (Boyce and Andrianopoulos, 2015)

Methods

Results

Conclusion