Biology subjects

Hess, P.

Publications and source records attributed to Hess, P..

5 recordsLinked to original sources

bioRxiv2025

Rho2 regulates granulocyte-triggered stress adaptation and cell wall remodeling in Aspergillus fumigatus

The airborne opportunistic fungal pathogen Aspergillus fumigatus poses a deadly threat to immunocompromised patients. Neutrophil granulocytes play a key role in the defense against invasive infections caused by this pathogen. The mechanisms by which Aspergillus defends itself against attacks by the immune system are only partially understood. Here we show that human granulocytes activate the cell wall integrity (CWI) pathway of A. fumigatus and that key components of the CWI such as the cell wall stress sensor MidA and the Rho GTPases Rho2 and Rho4 are important for the survival of Aspergillus hyphae under granulocyte attacks. A more detailed investigation of the role of Rho2 revealed that a mutant lacking rho2 is less virulent in a Galleria mellonella infection model. Overexpression of Rho2 increases the resistance of A. fumigatus hyphae to killing by granulocytes. While a mutant lacking Rho2 has a normal cell wall composition, overexpression or constitutive activation of Rho2 leads to an altered cell wall composition and impairs growths of the pathogen. The fungicidal effect of constitutive activation of Rho2 signaling, which correlates with the formation of cell wall chitin bulges, depends on the CWI MAP kinase MpkA. However, Rho2 itself does not appear to be a direct activator of the CWI MAP kinase module. Our results support a model where Rho2 in A. fumigatus actively counteracts granulocyte attacks by upregulating cell wall biosynthesis, thereby strengthening the cell wall and aiding the fungus in surviving the stress condition.

microbiology↗

bioRxiv2024

Effects of copepod chemical cues on intra- and extracellular toxins in two species of Dinophysis

Copepods may contribute to harmful algal bloom formation by selectively rejecting harmful cells. Additionally, copepods and the chemical cues they exude, copepodamides, have been shown to induce increased toxin production in paralytic and amnesic toxin producing microalgae. However, it is unknown if diarrhetic shellfish toxin (DST) producers such as Dinophysis respond to copepods or copepodamides in a similar fashion. Here we expose laboratory cultures of Dinophysis sacculus and D. acuminata to direct grazing by Acartia sp. copepods or copepodamides and measure their toxins after three days. Total Dinophysis- produced toxins (DPTs), okadaic acid, pectenotoxin-2, and C9-diol ester of okadaic acid, increased by 8 - 45% in D. sacculus but was significantly different from controls only in the highest (10 nM) copepodamide treatment whereas toxin content was not affected in D. acuminata. Growth rate was low across all groups and explained up to 91% of the variation in toxin content. DPTs were redistributed from internal compartments to the extracellular medium in the highest copepodamide treatments (5 - 10 nM), which were two to three times higher than controls and indicates an active release or passive leakage of toxins. Untargeted analysis of endometabolomes indicated significant changes in metabolite profiles for both species in response to the highest copepodamide treatments, independent of known toxins. However, it is not clear whether these are stress responses or caused by more complex mechanisms. The relatively small grazer-induced effect in Dinophysis observed here, compared to several species of Alexandrium and Pseudo-nitzschia reported previously, suggests that DPT production in Dinophysis is likely not induced by copepods, except perhaps in patches with high copepod densities. Thus, DPTs may, represent either a constitutive chemical defence for Dinophysis, or serve an altogether different purpose.

ecology↗

bioRxiv2023

Single cell and spatial alternative splicing analysis with long read sequencing

Long-read sequencing has become a powerful tool for alternative splicing analysis. However, technical and computational challenges have limited our ability to explore alternative splicing at single cell and spatial resolution. The higher sequencing error of long reads, especially high indel rates, have limited the accuracy of cell barcode and unique molecular identifier (UMI) recovery. Read truncation and mapping errors, the latter exacerbated by the higher sequencing error rates, can cause the false detection of spurious new isoforms. Downstream, there is yet no rigorous statistical framework to quantify splicing variation within and between cells/spots. In light of these challenges, we developed Longcell, a statistical framework and computational pipeline for accurate isoform quantification for single cell and spatial spot barcoded long read sequencing data. Longcell performs computationally efficient cell/spot barcode extraction, UMI recovery, and UMI-based truncation- and mapping-error correction. Through a statistical model that accounts for varying read coverage across cells/spots, Longcell rigorously quantifies the level of inter-cell/spot versus intra-cell/ spot diversity in exon-usage and detects changes in splicing distributions between cell populations. Applying Longcell to single cell long-read data from multiple contexts, we found that intra-cell splicing heterogeneity, where multiple isoforms co-exist within the same cell, is ubiquitous for highly expressed genes. On matched single cell and Visium long read sequencing for a tissue of colorectal cancer metastasis to the liver, Longcell found concordant signals between the two data modalities. Finally, on a perturbation experiment for 9 splicing factors, Longcell identified regulatory targets that are validated by targeted sequencing.

bioinformatics↗

bioRxiv2023

Niche differential gene expression analysis in spatial transcriptomics data identifies context-dependent cell-cell interactions

Single cells influence, and are shaped by, their local spatial niche. Technologies for in situ measurement of gene expression at the transcriptome scale have enabled the detailed profiling of the spatial distributions of cell types in tissue as well as the interrogation of local signaling patterns between cell types [1]. Towards these goals, we propose a new statistical procedure called niche-differential expression (niche-DE) analysis. Niche-DE identifies cell-type specific niche-associated genes, defined as genes whose expression within a specific cell type is significantly up- or down-regulated, in the context of specific spatial niches. We develop effective and interpretable measures for global false discovery control and show, through the analysis of data sets generated by myriad protocols, that the method is robust to technical issues such as over-dispersion and spot swapping. Niche-DE can be applied to low-resolution spot- and ROI-based spatial transcriptomics data as well as data that is single-cell or subcellular in resolution. Based on niche-DE, we also develop a procedure to reveal the ligand-receptor signaling mechanisms that underlie niche-differential gene expression patterns. When applied to 10x Visium data from liver metastases of colorectal cancer, niche-DE identifies marker genes for cancer-associated fibroblasts and macrophages and elucidates ligand-receptor crosstalk patterns between tumor cells, macrophages and fibroblasts. Co-detection by indexing (CODEX) was performed on the same patient samples, to corroborate the niche-DE results.

bioinformatics↗

bioRxiv2021

Deciphering microbiome impacts on fungal-microalgal interaction in a marine environment using metabolomics

The comprehension of microbial interactions is one of the key challenges in microbial ecology. The present study focuses on studying the chemical interaction between the toxic dinoflagellate Prorocentrum lima PL4V strain and associated fungal strains (two Penicillium sp. strains and three Aspergillus sp) among which the Aspergillus pseudoglaucus strain MMS1589 was selected for further co-culture experiment. Such rarely studied interaction (fungal-microalgal) was explored in axenic and non-axenic conditions, in a dedicated microscale marine environment (hybrid solid/liquid conditions), to delineate specialized metabolome alteration in relation to the P. lima and A. pseudoglaucus co-culture in regard to the presence of their associated bacteria. Such alteration was monitored by high-performance liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). In-depth analysis of the resulting data highlighted (1) the chemical modification associated to fungal-microalgal co-culture, and (2) the impact of associated bacteria in microalgal resilience to fungal interaction. Even if only a very low number of highlighted metabolites were fully characterised due to the poor chemical investigation of the studied species, a clear co-culture induction of the dinoflagellate toxins okadaic acid and dinophysistoxin 1 was observed. Such results highlight the importance to consider microalgal microbiome to study parameters regulating toxin production. Finally, a microscopic observation showed an unusual physical interaction between the fungal mycelium and the dinoflagellates.

microbiology↗