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Anne, S.

Publications and source records attributed to Anne, S..

3 recordsLinked to original sources

The Pseudogymnoascus destructans Proteome Under Copper Stress Conditions

The invasive fungal pathogen Pseudogymnoascus destructans is responsible for the collapse of several North American bat species through an infectious fungal skin disease known as White-Nose Syndrome (WNS). Recent transcriptomic studies have suggested that trace copper ion acquisition is essential for P. destructans propagation on its animal hosts. However, little is known about the mechanistic details of P. destructans adaptation occurring at the protein level. In this study, we report the global proteomic adaptation of P. destructans under chronic Cu-stress growth conditions employing chemically defined media. We identify 4340 P. destructans proteins, or approximately 47.8% of the predicted proteome, spanning a dynamic intensity range of six orders of magnitude. Chronic Cu-withholding stress leads to substantial alterations in the proteome, with 1398 differentially abundant proteins (DAPs) exhibiting statistically significant (p < 0.05) changes in protein levels compared to control growth conditions. We find that Cu-withholding stress induces increased levels of proteins associated with high-affinity Cu-acquisition, changes in intracellular superoxide dismutase (SOD) levels, and alterations in mitochondrial proteins related to aerobic respiration. In contrast, chronic Cu-overload stress leads to 390 DAPs (p < 0.05), which are more widely distributed across the proteome, with several DAPs associated with genomic stability and basic metabolism. Additionally, in this report, we present assessment of antisera products against intracellular and cell-surface protein targets of P. destructans that are effective for indicating Cu-withholding stress by western blotting.

microbiology↗

Pseudogymnoascus destructans transcriptional response to chronic copper stress

Copper (Cu) is an essential metal micronutrient, and a fungal pathogens ability to thrive in diverse niches across a broad range of bioavailable copper levels is vital for host-colonization and fungal-propagation. Recent transcriptomic studies have implemented that trace metal acquisition is important for the propagation of the white nose syndrome (WNS) causing fungus, Pseudogymnoascus destructans, on bat hosts. This report characterizes the P. destructans transcriptional response to Cu-withholding and Cu-overload stress. We identify 583 differently expressed genes (DEGs) that respond to Cu-withholding stress and 667 DEGs that respond to Cu-overload stress. We find that the P. destructans Cu-transporter genes CTR1a and CTR1b, as well as two homologs to Cryptococcus neoformans Cbi1/BIM1 VC83_03095 (BLP2) and VC83_07867 (BLP3) are highly regulated by Cu-withholding stress. We identify a cluster of genes, VC83_01834 - VC83_01837, that are regulated by copper bioavailability, which we identify as the Cu Responsive gene Cluster (CRC). We find that chronic exposure to elevated copper levels leads to an increase in genes associated with DNA repair and DNA replication fidelity. A comparison of our transcriptomic data sets with P. destructans at WNS fungal infection sites reveals several putative fungal virulence factors that respond to environmental copper stress.

molecular biology↗

Characterization of a High-Affinity Copper Transporter in the White-Nose Syndrome Causing Fungal Pathogen Pseudogym-noascus destructans

Copper is an essential micronutrient and the ability to scavenge tightly bound or trace levels of copper ions at the host-pathogen interface is vital for fungal proliferation in animal hosts. Recent studies suggest that trace metal ion acquisition is critical for the establishment and propagation of Pseudogymnoascus destructans, the fungal pathogen responsible for white-nose syndrome (WNS), on their bat host. However, little is known about these metal acquisition pathways in P. destructans. In this study, we report the characterization of the P. destructans high-affinity copper transporter VC83_00191 (PdCTR1a), which is implicated as a virulence factor associated with the WNS disease state. Using Saccharomyces cerevisiae as a recombinant expression host, we find that PdCTR1a localizes to the cell surface plasma membrane and can efficiently traffic Cu-ions into the yeast cytoplasm. Complementary studies in the native P. destructans fungus provide evidence that PdCTR1a transcripts and protein levels are dictated by Cu-bioavailability in the growth media. Our study demonstrates that PdCTR1a is a functional high-affinity copper transporter and is relevant to Cu-homeostasis pathways in P. destructans.

microbiology↗