Unraveling the Molecular Basis of Temperature-Dependent Genetic Regulation in Penicillium marneffei

Abstract

c Penicillium marneffei is an opportunistic fungal pathogen endemic in Southeast Asia, causing lethal systemic infections in immunocompromised patients. P. marneffei grows in a mycelial form at the ambient temperature of 25°C and transitions to a yeast form at 37°C. The ability to alternate between the mycelial and yeast forms at different temperatures, namely, thermal dimorphism, has long been considered critical for the pathogenicity of P. marneffei, yet the underlying genetic mechanisms remain elusive. Here we employed high-throughput sequencing to unravel global transcriptional profiles of P. marneffei PM1 grown at 25 and 37°C. Among ϳ11,000 protein-coding genes, 1,447 were overexpressed and 1,414 were underexpressed at 37°C. Counterintuitively, heat-responsive genes, predicted in P. marneffei through sequence comparison, did not tend to be overexpressed at 37°C. These results suggest that P. marneffei may take a distinct strategy of genetic regulation at the elevated temperature; the current knowledge concerning fungal heat response, based on studies of model fungal organisms, may not be applicable to P. marneffei. Our results further showed that the tandem repeat sequences (TRSs) are overrepresented in coding regions of P. marneffei genes, and TRS-containing genes tend to be overexpressed at 37°C. Furthermore, genomic sequences and expression data were integrated to characterize gene clusters, multigene families, and species-specific genes of P. marneffei. In sum, we present an integrated analysis and a comprehensive resource toward a better understanding of temperature-dependent genetic regulation in P. marneffei.

Expression and characterization of a Talaromyces marneffei active phospholipase B expressed in a Pichia pastoris expression system

“…24 Our previous comparative transcriptomic analysis (unpublished data) has indicated that the TmPlb1 gene is overexpressed in the yeast phase (1.60-fold). In this study, sensitive qRT-PCR was used to analyze the differential expression of TmPlb1 between the mycelial phase and yeast phase, and the results confirmed that the mRNA level of TmPlb1 increased in the pathogenic yeast phase (1.85-fold).…”

Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogenHistoplasma capsulatum

“…6). In all cases where RNAseq data was available [3, 4, 45–47] (S6 Data), the distribution of yeast/hyphal expression for the orthologs of the filament-associated genes was biased towards showing hyphal expression rather than mimicking the distribution of the global transcriptome (p < .05, Wilcoxon test; S7 Data). In contrast, in Ophiostoma novo-ulmi (the causative agent of Dutch elm disease and the only other dimorphic ascomycete for which we were able to obtain RNAseq data [48]), the distribution of yeast/hyphal expression for the filament-associated regulon was indistinguishable from the rest of the transcriptome.…”

The novelDblhomology/BAR domain protein, MsgA, ofTalaromyces marneffeiregulates yeast morphogenesis during growth inside host cells

“…A recent study of the genome structure of T . marneffei identified an increase in number of genes with TRSs compared to three other pathogenic and non-pathogenic filamentous fungi (Yang et al 2013).…”