Project description:Lysine acetylation is critical in regulating important biological processes in many organisms, yet little is known about acetylome evolution and its contribution to phenotypic diversity. Here, we compare the acetylomes of baker’s yeast and the three deadliest human fungal pathogens, Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus. Using mass spectrometry enriched for acetylated peptides together with public data from Saccharomyces cerevisiae, we show that fungal acetylomes are characterized by dramatic evolutionary dynamics and limited conservation in core biological processes. Notably, the levels of protein acetylation in pathogenic fungi correlate with their pathogenicity. Using gene knockouts and pathogenity assays in mice, we identify deacetylases with critical roles in virulence and protein translation elongation. Finally, through mutational analysis of deactylation motifs we find evidence of positive selection at specific acetylation motifs in fungal pathogens. These results shed new light on the pathogenicity regulation mechanisms underlying the evolution of fungal acetylomes.
Project description:The “Amoeboid Predator-Fungal Animal Virulence Hypothesis” posits that interactions with environmental phagocytes shape the evolution of virulence traits in fungal pathogens. In this hypothesis, selection to avoid predation by amoeba inadvertently selects for traits that contribute to fungal escape from phagocytic immune cells. Here, we investigate this hypothesis in the human fungalpathogens Cryptococcus neoformans and Cryptococcus deneoformans. Applying quantitative trait locus (QTL) mapping and comparative genomics, we discovered a cross-species QTL region that is responsible for variation in resistance to amoeba predation. In C. neoformans, this same QTL was found to have pleiotropic effects on melanization, an established virulence factor. Through fine mapping and population genomic comparisons, we identified the gene encoding the transcription factor BZP4 that underlies this pleiotropic QTL and we show that decreased expression of this gene reduces melanization and increases susceptibility to amoeba predation. Despite the joint effects of BZP4 on amoeba resistance and melanin production, we find no relationship between BZP4 genotype and escape from macrophages or virulence in murine models of disease. Our findings provide new perspectives on how microbial ecology shapes the genetic architecture of fungal virulence, and suggests the need for more nuanced models for the evolution of pathogenesis that account for the complexities of both microbe-microbe and microbe-host interactions.
Project description:We applied single-cell spatial transcriptomics (Xenium, 10X genomics) to reveal the lung wall landscape from healthy donors, patients with asthma undergoing anti-inflammatory therapies and historical clinical trial samples.
2025-04-08 | GSE269354 | GEO
Project description:Melbourne Genomics Health Alliance 'Controlling Superbugs' Study - Using genomics to track transmission of multidrug-resistant pathogens in hospitals
| PRJNA565795 | ENA
Project description:Soil microbiome after 15 years of agricultural intensification (FUNGI)
| PRJNA1362405 | ENA
Project description:Soil microbiome after 15 years of agricultural intensification (PROKARYOTA)
Project description:In opportunistic human pathogenic fungi, changes in gene expression play a crucial role in the evolution of growth stages from early spore germination through host infection. Comparative transcriptomics from diverse fungal pathogens along closely related non-pathogenic model provided insights of regulatory mechanisms behind the initiation of infectious processes by different fungi. We examined the gene expression patterns of 3,845 single-copy orthologous genes (SCOGs) across five phylogenetically distinct species, including the opportunistic human pathogens Fusarium oxysporum, Aspergillus fumigatus, and A. nidulans, and nonpathogenic species Neurospora crassa and Trichoderma asperelloides, at four sequential stages spore germination.