Cell-type-specific transcriptional profiles of the dimorphic pathogen Penicillium marneffei reflect distinct reproductive, morphological, and environmental demands

• Published in: G3 : genes - genomes - genetics Vol. 3; no. 11; pp. 1997 - 2014
• Main Authors: Pasricha, Shivani, Payne, Michael, Canovas, David, Pase, Luke, Ngaosuwankul, Nathamon, Beard, Sally, Oshlack, Alicia, Smyth, Gordon K, Chaiyaroj, Sansanee C, Boyce, Kylie J, Andrianopoulos, Alex
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01-11-2013
• Subjects: Antifungal Agents - pharmacology; Cluster Analysis; Ergosterol - metabolism; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression Regulation, Fungal - drug effects; Genome, Fungal; Humans; Investigations; Membrane Fluidity; Oligonucleotide Array Sequence Analysis; Penicillium - drug effects; Penicillium - genetics; Penicillium - growth & development; Sequence Analysis, DNA; Temperature; Transcriptome - drug effects; Penicillium marneffei; microarray; Talaromyces marneffei; dimorphic switch; hyphae; cell wall; conidiation; yeast
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1534/g3.113.006809

Penicillium marneffei is an opportunistic human pathogen endemic to Southeast Asia. At 25° P. marneffei grows in a filamentous hyphal form and can undergo asexual development (conidiation) to produce spores (conidia), the infectious agent. At 37° P. marneffei grows in the pathogenic yeast cell form that replicates by fission. Switching between these growth forms, known as dimorphic switching, is dependent on temperature. To understand the process of dimorphic switching and the physiological capacity of the different cell types, two microarray-based profiling experiments covering approximately 42% of the genome were performed. The first experiment compared cells from the hyphal, yeast, and conidiation phases to identify "phase or cell-state-specific" gene expression. The second experiment examined gene expression during the dimorphic switch from one morphological state to another. The data identified a variety of differentially expressed genes that have been organized into metabolic clusters based on predicted function and expression patterns. In particular, C-14 sterol reductase-encoding gene ergM of the ergosterol biosynthesis pathway showed high-level expression throughout yeast morphogenesis compared to hyphal. Deletion of ergM resulted in severe growth defects with increased sensitivity to azole-type antifungal agents but not amphotericin B. The data defined gene classes based on spatio-temporal expression such as those expressed early in the dimorphic switch but not in the terminal cell types and those expressed late. Such classifications have been helpful in linking a given gene of interest to its expression pattern throughout the P. marneffei dimorphic life cycle and its likely role in pathogenicity.