title: Role of the rttA gene in morphogenesis, stress response, and virulence in the human pathogenic fungus Penicillium marneffei.
abstract: Penicillium marneffei is a human pathogenic fungus and the only thermally dimorphic species of the genus. At 25°C, P. marneffei grows as a mycelium that produces conidia in chains. However, when incubated at 37°C or following infection of host tissue, the fungus develops as a fission yeast. Previously, a mutant (strain I133) defective in morphogenesis was generated via Agrobacterium-mediated transformation. Specifically, the rtt109 gene (subsequently designated rttA) in this mutant was interrupted by T-DNA insertion. We characterized strain I133 and the possible roles of the mutated rttA gene in altered P. marneffei phenotypes. At 25°C, the rttA mutant produces fewer conidia than the wild type and a complemented mutant strain, as well as slower rates of conidial germination; however, strain I133 continued to grow as a yeast in 37°C-incubated cultures. Furthermore, whereas the wild type exhibited increased expression of rttA at 37°C in response to the DNA-damaging agent methyl methane sulfonate, strain I133 was hypersensitive to this and other genotoxic agents. Under similar conditions, the rttA mutant exhibited decreased expression of genes associated with carbohydrate metabolism and oxidative stress. Importantly, when compared with the wild-type and the complemented strain, I133 was significantly less virulent in a Galleria infection model when the larvae were incubated at 37°C. Moreover, the mutant exhibited inappropriate phase transition in vivo. In conclusion, the rttA gene plays important roles in morphogenesis, carbohydrate metabolism, stress response, and pathogenesis in P. marneffei, suggesting that this gene may be a potential target for the development of antifungal compounds.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai.
authors.forename: Sumanun
authors.initials: S
authors.lastname: Suwunnakorn
authors.affiliation: Center for Applied Chemical Biology and Department of Biological Sciences, Youngstown State University, One University Plaza, Youngstown, Ohio, USA.
authors.forename: Chester R
authors.initials: CR
authors.lastname: Cooper
authors.affiliation: Division of Clinical Microbiology, Department of Medical Technology, School of Allies Health Sciences, University of Phayao.
authors.forename: Aksarakorn
authors.initials: A
authors.lastname: Kummasook
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai.
authors.forename: Monsicha
authors.initials: M
authors.lastname: Pongpom
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 drnongnuch@gmail.com.
authors.forename: Nongnuch
authors.initials: N
authors.lastname: Vanittanakom
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D055786:Gene Knockout Techniques; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D007915:Lepidoptera / Q000382:microbiology; D016254:Mutagenesis, Insertional; D010407:Penicillium / Q000166:cytology / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D013312:Stress, Physiological; D013696:Temperature; D014774:Virulence
keywords: DNA damage response; Penicillium marneffei; dimorphic fungus; rttA (rtt109); virulence