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Heeren, S.

Publications and source records attributed to Heeren, S..

6 recordsLinked to original sources

Genomic evidence for co-evolution and sporadic host shifts in leishmaniaviruses

The association between Leishmania parasites and the double-stranded RNA virus, Leishmaniavirus (LRV), significantly impacts human health by modulating disease severity. Despite its clinical importance, the evolutionary history of this symbiosis remains largely unknown. This study presents one of the first formal investigations of their co-phylogenetic history across different taxonomic hierarchical levels; based on total RNA sequencing of cultivated isolates, simultaneously capturing the parasite`s transcriptome and the viral genome. We found strong support for phylogenetic congruence between Leishmania and LRV at both the subgenus and species level; based on genetic distance correlations and formal co-phylogenetic statistics. Focusing on the interactions of L. (V.) braziliensis and L. (V.) guyanensis with LRV1, we observed weaker co-phylogenetic signals though frequent instances of intraspecific host switching. Together, our findings indicate that LRV has been a persistent evolutionary partner of Leishmania, providing a framework for understanding the emergence and maintenance of virus-mediated disease phenotypes.

evolutionary biology↗

Direct genome sequencing of Leishmania tropica in tissues of Moroccan patients with cutaneous leishmaniasis reveals micro-focal transmission underlain by clonal and sexual reproduction modes

Leishmania tropica is causing cutaneous leishmaniasis (CL) from North Africa to India and in Ethiopia and is reported to be transmitted from humans to humans through sand fly bites. While this species is characterized by a high genetic diversity all over the area of endemicity, there is very little information on diversity at micro-epidemiological scale. Here, we zoomed on an epidemic Moroccan focus of CL - restricted in space and time - and studied transmission patterns by comparative genomics of parasites in human patients. We used a culture-independent method of genome sequencing based on Leishmania genome capture (SureSelect-sequencing, SuSL-seq), applied directly on dermal scrapings. We first compared the genome of paired samples: i.e. parasites in host tissues analyzed by SuSL-seq and derived isolates shortly maintained in culture and analyzed by whole genome sequencing (WGS). Despite the low passage number of isolates, significant differences were observed between karyotypes of 4/7 paired samples, highlighting the clinical and epidemiological relevance of direct genome sequencing. Secondly, we identified 7 groups of nearly identical genotypes, characteristic of clonal propagation as well as parasites with mixed ancestry, a signature of genetic exchange. Our results reveal a micro-focal transmission among humans, underlain by clonal and sexual reproductive modes. This study demonstrates the power of direct genome sequencing for evolutionary genetics at a micro-epidemiological scale.

genomics↗

Evolutionary genomics of a zoonotic parasite across the Neotropical Realm

The Neotropical realm, one of the most biodiverse regions on Earth, houses a broad range of zoonoses that pose serious public health threats. Protozoan parasites of the Leishmania (Viannia) braziliensis species complex cause zoonotic leishmaniasis in Latin America with clinical symptoms ranging from simple cutaneous to destructive, disfiguring mucosal lesions. We present the first comprehensive genome-wide continental study including 257 cultivated isolates representing most of the geographical distribution of this major human pathogen. The L. braziliensis species complex is genetically highly heterogeneous, consisting of divergent parasite groups that are associated with different environments and vary greatly in diversity. Apart from several small ecologically isolated groups with little diversity, our sampling identifies two major parasite groups, one associated with the Amazon and the other with the Atlantic Forest biomes. These groups show different recombination histories, as suggested by high levels of heterozygosity and effective population sizes in the Amazonian group in contrast to high levels of linkage and clonality in the Atlantic group. We argue that these differences are linked to strong eco-epidemiological differences between the two regions. In contrast to geographically focused studies, our study provides a broad understanding of the molecular epidemiology of zoonotic parasites circulating in tropical America.

evolutionary biology↗

Parasite hybridization promotes spreading of endosymbiotic viruses

Viruses are the most abundant biological entities on Earth and play a significant role in the evolution of many organisms and ecosystems. In pathogenic protozoa, the presence of endosymbiotic viruses has been linked to an increased risk of treatment failure and severe clinical outcome. Here, we studied the molecular epidemiology of the zoonotic disease cutaneous leishmaniasis in Peru and Bolivia through a joint evolutionary analysis of Leishmania braziliensis parasites and their endosymbiotic Leishmania RNA virus. We show that parasite populations circulate in isolated pockets of suitable habitat and are associated with single viral lineages that appear in low prevalence. In contrast, groups of hybrid parasites were geographically and ecologically dispersed, and commonly infected from a pool of genetically diverse viruses. Our results suggest that parasite hybridization, likely due to increased human migration and ecological perturbations, increased the frequency of endosymbiotic interactions known to play a key role in disease severity.

evolutionary biology↗

Genome diversity of Leishmania aethiopica

Leishmania aethiopica is a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure, L. aethiopica is the most neglected species of the Leishmania genus in terms of scientific attention. Here, we explored the genome diversity of L. aethiopica by analyzing the genomes of twenty isolates from Ethiopia. Phylogenomic analyses identified two strains as interspecific hybrids involving L. aethiopica as one parent and L. donovani and L. tropica respectively as the other parent. High levels of genome-wide heterozygosity suggest that these two hybrids are equivalent to F1 progeny that propagated mitotically since the initial hybridization event. Analyses of allelic read depths further revealed that the L. aethiopica - L. tropica hybrid was diploid and the L. aethiopica - L. donovani hybrid was triploid, as has been described for other interspecific Leishmania hybrids. When focusing on L. aethiopica, we show that this species is genetically highly diverse and consists of both asexually evolving strains and groups of recombining parasites. A remarkable observation is that some L. aethiopica strains showed an extensive loss of heterozygosity across large regions of the chromosomal genome, which likely arose from gene conversion/mitotic recombination. Hence, our prospection of L. aethiopica genomics revealed new insights into the genomic consequences of both meiotic and mitotic recombination in Leishmania.

genomics↗

Lifestyle and not density of fish hosts determines parasite distribution over time and space

Despite their important ecological role, questions remain on mechanisms structuring parasite assemblages. We present a simple and endemic host-parasite system of clupeid fishes and monogenean parasites (Kapentagyrus, Dactylogyridae) with contrasting levels of host-specificity from Lake Tanganyika as a model to study parasite distribution patterns and co-infection dynamics in nature. With two parasites, two host species, and three host-parasite combinations between them, this unique system represents the simplest natural host-parasite model that is not trivial. We modelled spatiotemporal dynamics of host-parasite interaction using infection data along the North-South axis of Lake Tanganyika (660 km) over the course of two seasons and four years (1730 fish, 3710 parasites). We found temporal stability of infection, which contrasts with previously reported seasonally driven fluctuations of fish host abundances. We found a difference in spatial structure between the parasite species, confirming that their distributions are only restricted by their most mobile host species. On the host species that is infected by two parasite species, we discovered a positive correlation with host body size for one parasite species, and a negative correlation for the other species. As we also discovered facilitation of infection, this cannot be due to competition. The differences reported between parasite species infecting the same host species further extrapolate the dependence on changes in lifestyle of the host during its ontogenetic development. In conclusion, we show that in a simple, closed system parasite infection dynamics are dependent on a combination of host mobility, host lifestyle changes over ontogenetic development and interspecific interactions between parasites.

ecology↗