Biology subjects

Dumetz, F.

Publications and source records attributed to Dumetz, F..

9 recordsLinked to original sources

bioRxiv2026

Strain-level diversity shapes competitive outcomes in Fusarium: a multi-omic synthesis of fungal warfare

Fusarium head blight (FHB) is driven by co-occurring Fusarium species. Yet the molecular bases of their competitive interactions, particularly at the strain level, remain largely unknown. We performed an integrated multi-omic investigation of four Fusarium isolates cultivated in monoculture, self-confrontation (SC) and inter-specific confrontation (C) assays: two Fusarium graminearum strains FgrI349 and FgrPH-1, and two Fusarium avenaceum strains FaveI494 and FaLH03. Light microscopy and quantitative colorimetry revealed marked phenotypic heterogeneity. the F. graminearum strains formed expansive, red-pigmented colonies with rapid radial growth, whereas the F. avenaceum isolates grew more slowly and displayed distinct colony morphologies and pigmentation patterns. Untargeted LC-HRMS detected 1,008 metabolites in monocultures and 938 metabolites in confrontation zones. Species-level chemical signatures were confirmed, and strain-specific metabolite sets were identified, with FaLH03 producing more than 60 % of the metabolites being made exclusively by a single strain, highlighting its exceptionally unique metabolic profile. RNA-seq uncovered extensive transcriptional reprogramming during competition. In self-confrontations, strain-specific differences persisted but no major morphological or metabolic shifts were observed. Inter-specific confrontations elicited partner-dependent responses: FgrI349 up-regulated 1,492 genes against FaveI494 (including secondary-metabolite biosynthesis, oxidoreductase activity and transport) but only 407 genes against FaLH03, while down-regulating secondary-metabolite genes in the conspecific confrontation. Conversely, the F. avenaceum isolates showed opposite trends; FaLH03 strongly repressed ribosome-biogenesis and cell-wall genes while inducing oxidative-metabolism pathways, whereas FaveI494 displayed a modest transcriptional response dominated by down-regulation of cell-division and chromosome-segregation genes. Gene-ontology enrichment highlighted an opponent-specific reversal of the secondary-metabolite biosynthetic process category in F. graminearum: down-regulated in intra-specific confrontation but up-regulated in both inter-specific encounters. Collectively, our results demonstrate that competitive outcomes are shaped more by strain identity than by species identity, with each strain deploying a distinct molecular arsenal, ranging from metabolite-mediated antagonism to targeted transcriptional shutdown, when confronted with a specific opponent. These findings refine our understanding of Fusarium community dynamics and provide a framework for developing strain-targeted biocontrol strategies against FHB.

microbiology↗

bioRxiv2026

Hi-C data from the filamentous fungus Podospora anserina and associated 3D models to visualize the spatial organization of its chromosomes

ObjectivesModel species are essential for fundamental research in biology. While a complete genomic sequence is a prerequisite for genetic studies, it is not enough on its own. Understanding the three-dimensional organization of the genome is also important, allowing researchers to gain a more realistic understanding of the mechanisms governing genome function. In the fungal model Podospora anserina, although the genomic sequence has been established for a long time, the three-dimensional organization remained unknown. Here we obtained the first Hi-C datasets and present associated 3D models, providing the research community with a valuable resource for better multi-omics data integration. Data descriptionHi-C experiments were performed in duplicate, using nuclei purified from wild-type fungal mycelium. Four FASTQ files were obtained (two per replicate) and used as inputs for the 3DGB workflow with four different output resolutions, to observe the genome organization of P. anserina at different levels of detail (50 kb, 20 kb, 10 kb, and 5 kb). In a context where researchers already have, for this species, a large amount of traditional omics data (ChIP-seq, RNA-seq, etc.), these 3D models are helpful for complementing the linear representation of the genome, which is traditionally used in bioinformatic analyses.

genomics↗

bioRxiv2026

Stage-aware transcriptomics reveals selective haplotype persistence in short-term ex vivo cultured Plasmodium vivax

Plasmodium vivax (Pv) infections are developmentally asynchronous and often polyclonal, complicating interpretation of bulk parasite transcriptomes. Here, we analyzed paired in vivo and short-term ex vivo transcriptomes from Ethiopian clinical isolates using stage deconvolution and PvMSP1 haplotyping. Ex vivo maturation modestly increased inferred schizont representation while largely preserving the proportion of trophozoites and gametocytes. After adjustment for parasite stage composition, in vivo and ex vivo transcriptomes remained globally similar, with no genes significantly differentially expressed, indicating the absence of major culture-induced transcriptional response. In contrast, short-term culture reduced multiplicity of infection, contracted within-host haplotype diversity, and non-randomly depleted specific haplotypes, consistent with a clonal bottleneck. In a subset of low-complexity infections, residual expression patterns were clustered by dominant haplotype, suggesting genotype-associated transcriptional heterogeneity independent of developmental stage. Together, these findings indicate that short-term ex vivo culture enriches late asexual stages and selectively filters clones rather than inducing a common transcriptional program. These results shows that ex vivo cultures are reliable way to study gene expression, especially for late stages. However, these needs explicitly model developmental composition and infection complexity when interpreting Pv transcriptomes from natural infections Author summaryMalaria caused by Plasmodium vivax is difficult to study because this parasite cannot yet be grown continuously in the laboratory and infections in patients often contain parasites at different developmental stages and multiple parasite lineages at the same time. In this study, we wanted to understand how much of the parasite gene-expression signal reflects true biological differences, and how much is explained by parasite development or changes that occur during short-term laboratory maturation. We compared parasites collected directly from patients in Ethiopia with matched parasite matured briefly outside the body. We found that short-term culture mainly increased the proportion of later-stage parasites, but after accounting for developmental stage, the overall gene-expression patterns remained very similar. However, culture reduced the diversity of parasite lineages within infections, suggesting that some parasite lineages survive better than others under laboratory conditions. Our findings highlight that natural Pv infections are complex mixtures of parasite stages and lineages. Accounting for this complexity will improve how researchers interpret parasite gene-expression studies and design future studies of parasite invasion, transmission, and survival.

cell biology↗

bioRxiv2026

MaRNAV-1 infection of Plasmodium vivax is associated with increased parasite transmission and host inflammatory responses

MaRNAV-1 is an RNA virus recently identified in Plasmodium vivax-infected samples, but definitive evidence that it infects the parasite and influences malaria pathogenesis remains unknown. Here, we demonstrate that MaRNAV-1 is an intracellular virus that is present in P. vivax at various stages of its life cycle, including blood, sporozoite, and liver stages. Viral prevalence varied geographically between Cambodian and Ethiopian parasites. MaRNAV-1 presence and load were positively associated with parasite transmission potential, as reflected by increased gametocyte abundance and higher oocyst prevalence and intensity in membrane feeding assays. MaRNAV-1 loads were higher in symptomatic compared to asymptomatic infections, and higher MaRNAV-1 loads were associated with elevated body temperature, independently of parasitemia. MaRNAV-1 infection elicits an antibody response and is associated with dendritic cell activation, a shift from Th2 to a Th1-driven immune response, and an increased frequency of double-negative B cells. Accordingly, MaRNAV-1-infected patients had higher concentrations of circulating cytokines, such as IFN-{gamma}, CXCL10, IL-1RA, and IL-6, independently of parasitemia. Together, these findings demonstrate that MaRNAV-1 is a genuine parasite-infecting virus associated with increased parasite transmission potential and with modulation of clinical outcomes in, and host immune response to, P. vivax infections. Our study broadens the conventional view of host-pathogen interactions in malaria by revealing complex virus-parasite-host relationships.

microbiology↗

bioRxiv2025

The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures

Leishmania spp. regulate gene expression largely post-transcriptionally, yet untranslated regions (UTRs) remain poorly delineated. We generated high-quality genome and transcriptome datasets for Leishmania donovani strain 1S2D (Ld1S) by combining PacBio HiFi de novo assembly with Oxford Nanopore direct RNA sequencing of promastigotes and axenic amastigotes. The genome assembly consists of 65 scaffolds totaling [~]33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including some reshufling genes among polycistronic transcription units and validated by polycistronic reads from RNA sequencing. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in UTRs. We also noted that 31.9% and 11.5% were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a comprehensive annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms, and, overall, points to an important role of 3 UTR in post-transcriptional regulation in L. donovani. Author SummaryLeishmania donovani parasites cause visceral leishmaniasis, a deadly disease affecting hundreds of thousands of people worldwide. Unlike most eukaryotes, these parasites do not regulate their genes mainly at the level of transcription. Instead, control happens after the genes are transcribed, and much of this regulation depends on regions of RNA that are not translated into protein, called untranslated regions (UTRs). However, UTRs in Leishmania have remained poorly characterized. Here we generated high-quality genome and transcriptome resources for a clinical strain of L. donovani. By combining state-of-the-art long-read sequencing technologies, we precisely mapped thousands of UTRs and discovered that many genes produce transcripts with variable UTR lengths that differ between parasite life stages. We also found that UTRs are enriched in RNA structures called G-quadruplexes, which are known to influence gene regulation. These findings provide the most comprehensive view to date of UTRs in Leishmania and highlight their central role in controlling how genes are expressed during the parasites life cycle. Our work lays a foundation for future studies aimed at understanding parasite biology and identifying new targets for intervention.

genomics↗

bioRxiv2025

Degradation of ribosomal RNA during Plasmodium falciparum gametocytogenesis

The life cycle of Plasmodium falciparum is characterized by complex regulatory changes that allow adaptation of the parasites to different environmental conditions, which are especially pronounced during transmission between the mammalian host and the insect vector. Previous studies have shown that P. falciparum uses three types of ribosomal RNAs (rRNA A-, S1- and S2-types) at different stages of its life cycle. We used Oxford Nanopore Technologies (ONT) direct RNA sequencing to investigate the dynamics of rRNA usage throughout the parasites intraerythrocytic development, as well as in salivary gland sporozoites. Our study revealed a preponderance of A-type rRNAs during the intraerythrocytic cycle and gametocytogenesis, while S-type rRNAs slowly increase in abundance in mosquito stages starting three days post infection. Salivary gland sporozoites showed an even proportion of all rRNA types. By examining the length distributions of rRNA molecules, we detected an extensive and specific degradation of rRNAs during gametocytogenesis, starting in stage II gametocytes and continuing until the final stages of gametocyte development. We hypothesize that rRNA degradation may be linked to the global translational repression and metabolic quiescence described in stage V gametocytes, similar to mechanisms observed in bacterial and eukaryotic stress responses.

microbiology↗

bioRxiv2021

The in vivo RNA structurome of the malaria parasite Plasmodium falciparum, a protozoan with an A/T-rich transcriptome

Plasmodium falciparum, a protozoan parasite and causative agent of human malaria, has one of the most A/T-biased genomes sequenced to date. This may give the genome and the transcriptome unusual structural features. Recent progress in sequencing techniques has made it possible to study the secondary structures of RNA molecules at the transcriptomic level. Thus, in this study we produced the in vivo RNA structurome of a protozoan parasite with a highly A/U-biased transcriptome. We showed that it is possible to probe the secondary structures of P. falciparum RNA molecules in vivo using two different chemical probes, and obtained structures for more than half of all transcripts in the transcriptome. These showed greater stability (lower free energy) than the same structures modelled in silico, and structural features appeared to influence translation efficiency and RNA decay. Finally, we compared the P. falciparum RNA structurome with the predicted RNA structurome of an A/T-balanced species, P. knowlesi, finding a bias towards lower overall transcript stability and more hairpins and multi-stem loops in P. falciparum. This unusual protozoan RNA structurome will provide a basis for similar studies in other protozoans and also in other unusual genomes.

microbiology↗

bioRxiv2021

G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum

G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified the formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.

microbiology↗

bioRxiv2019

C-5 DNA methyltransferase 6 does not generate detectable DNA methylation in Leishmania

Cytosine C5 methylation is an important epigenetic control mechanism in a wide array of Eukaryotic organisms and generally carried out by proteins of C-5 DNA methyltransferase family (DNMTs). In several protozoans the status of this mechanism remains elusive, such as in Leishmania, the causative agent of the disease leishmaniasis in humans and a wide array of vertebrate animals. In this work, we show that the Leishmania donovani genome contains a C-5 DNA methyltransferase (DNMT) from the DNMT6 subfamily, of which the function is still unclear, and verified its expression at RNA level. We created viable overexpressor and knock-out lines of this enzyme and characterised their genome-wide methylation patterns using whole-genome bisulfite sequencing, together with promastigote and amastigote control lines. Interestingly, despite DNMT6 presence, we found that methylation levels were equal to or lower than 0.0003% at CpG sites, 0.0005% at CHG sites and 0.0126% at CHH sites at genome scale. As none of the methylated sites were retained after manual verification, we conclude that there is no evidence for DNA methylation in this species. We demonstrate that this difference in DNA methylation between the parasite (no detectable DNA methylation) and the vertebrate host (DNA methylation), allows enrichment of parasite versus host DNA using Methyl-CpG-binding domain columns, readily available in commercial kits. As such, we depleted methylated DNA from mixes of Leishmania promastigote and amastigote DNA with human DNA, resulting in average Leishmania:human enrichments from 62x up to 263x. These results open a promising avenue for unmethylated DNA enrichment as a pre-enrichment step before sequencing Leishmania clinical samples.

molecular biology↗