title: Functional analysis of atfA gene to stress response in pathogenic thermal dimorphic fungus Penicillium marneffei.
abstract: 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.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Panjaphorn
authors.initials: P
authors.lastname: Nimmanee
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, Research Centre of Infection and Immunology and Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
authors.forename: Patrick C Y
authors.initials: PC
authors.lastname: Woo
authors.affiliation: Faculty of Medicine, University of Phayao, Phayao, Thailand.
authors.forename: Pramote
authors.initials: P
authors.lastname: Vanittanakom
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sirida
authors.initials: S
authors.lastname: Youngchim
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nongnuch
authors.initials: N
authors.lastname: Vanittanakom
mesh_terms: D051696:Activating Transcription Factors / Q000235:genetics*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D002686:Chitin / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D005816:Genetic Complementation Test; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D050296:Microbial Viability / Q000235:genetics / Q000276:immunology; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000235:genetics; D010407:Penicillium / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D013312:Stress, Physiological / Q000235:genetics*; D013696:Temperature; D014466:Ultraviolet Rays
chemical_list: D051696:Activating Transcription Factors; D005656:Fungal Proteins; D002686:Chitin