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Penicillium marneffei , the pathogenic thermal dimorphic fungus is a causative agent of a fatal systemic disease, penicilliosis marneffei, in immunocompromised patients especially HIV patients. For growth and survival, this fungus has to adapt to environmental stresses outside and inside host cells and this adaptation requires stress signaling pathways and regulation of gene expression under various kinds of stresses. In this report,  P. marneffei  activating transcription factor ( atfA ) gene encoding bZip-type transcription factor was characterized. To determine functions of this gene,  atfA  isogenic mutant strain was constructed using the modified split marker recombination method. The phenotypes and susceptibility to varieties of stresses including osmotic, oxidative, heat, UV, cell wall and cell membrane stresses of the mutant strain were compared with the wild type and the  atfA  complemented strains. Results demonstrated that the mRNA expression level of  P. marneffei atfA  gene increased under heat stress at 42°C. The  atfA  mutant was more sensitive to sodium dodecyl sulphate, amphotericin B and  tert -butyl hydroperoxide than the wild type and complemented strains but not hydrogen peroxide, menadione, NaCl, sorbitol, calcofluor white, itraconazole, UV stresses and heat stress at 39°C. In addition, recovery of  atfA  mutant conidia after mouse and human macrophage infections was significantly decreased compared to those of wild type and complemented strains. These results indicated that the  atfA  gene was required by  P. marneffei  under specific stress conditions and might be necessary for fighting against host immune cells during the initiation of infection.

Functional Analysis of atfA Gene to Stress Response in Pathogenic Thermal Dimorphic Fungus Penicillium marneffei