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Schaer, J.

Publications and source records attributed to Schaer, J..

4 recordsLinked to original sources

The Monophyly of Nycteria and Polychromophilus Parasites A Missing Piece in the Evolution of Malaria and Other Haemosporida

Haemosporida is a diverse order of vector-borne apicomplexan parasites infecting terrestrial vertebrates worldwide, including humans, but the evolutionary relationships among its genera remain unresolved. The phylogenetic placement of two bat-restricted genera, Nycteria and Polychromophilus, both of which lack erythrocytic schizogony, has varied across studies depending on taxon sampling and marker choice. To address this problem, an expanded dataset of near-complete mitochondrial (mtDNA) genomes together with nine nuclear loci were analyzed. Phylogenetic analyses of mtDNA recovered Nycteria and Polychromophilus as a strongly supported monophyletic clade. In contrast, analyses based only on the three mitochondrial coding genes (CDS) or a reduced nuclear dataset failed to recover their monophyly and showed low support and extensive topological conflict at deeper nodes. These results indicate that near-complete mitochondrial genomes recover phylogenetic signal that is not captured by reduced mitochondrial coding sequences or partial nuclear datasets. Molecular dating analyses further showed that divergence estimates for a putative Nycteria-Polychromophilus clade are compatible with the proposed times for bats diversification, and consistent with the broader haemosporidian timescale. When the Nycteria-Polychromophilus clade was incorporated as a calibration prior, divergence-time estimates became more precise without altering the overall evolutionary timeframe. Substantial mitochondrial gene-order rearrangements in a distinct Nycteria lineage were confirmed, highlighting structural divergence within this bat-associated group. In addition, heterogeneity in rates across mtDNA haemosporidian lineages was observed. Together, these findings support the existence of a distinct bat-associated clade whose deeper placement and evolutionary significance should be tested with broader phylogenomic sampling. Author SummaryMalaria parasites belong to a diverse group of organisms that infect many kinds of vertebrates, including birds, reptiles, and mammals (such as humans). Understanding how these parasites are related to each other is important for explaining how key biological traits have evolved. However, the relationships among major groups of haemosporidian parasites, including malaria parasites, remain unclear, particularly for those infecting bats. In this study, we focused on two groups of bat parasites, Nycteria and Polychromophilus, which share unusual biological features. The inferred evolutionary relationships of these two genera to other haemosporidians have been inconsistent across previous studies. By analyzing near-complete mitochondrial genomes, we found strong evidence that these two groups descended from a common evolutionary ancestor. In contrast, smaller datasets including nuclear genes failed to recover this relationship and produced conflicting results, suggesting that they lack sufficient information to resolve deep evolutionary relationships. We also found that this bat-associated lineage likely originated around the same time as early bats. In addition, we identified structural changes in the mitochondrial genome of one lineage, highlighting its evolutionary distinctiveness. Together, our results suggest that bats host a unique group of malaria parasites and demonstrate that more complete genetic data are essential for resolving their evolutionary history.

evolutionary biology↗

Engraftment of donor phageome via fecal microbiota transplantation in recurrent C. difficile infection: a prospective observational study

1The high efficacy of fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) is often attributed to the restoration of the bacterial community. However, factors beyond bacteria, such as bacteriophages (phages), may also play a critical role in FMTs success. We aimed to evaluate the preservation of the phage community (phageome) along the FMT production process following Good Manufacturing Practices (GMP) at the Lausanne University Hospital (CHUV), and the engraftment of the phages in patients receiving FMT to treat rCDI. Samples from one donor were used to test the need for amplification and to compare spin-column versus magnetic bead purification. Then, sixteen samples, from four donations of a second healthy donor, were collected at various production stages - fresh, frozen, homogenized, and encapsulated - for phageome analysis. The phage community profiles of three patients before, at 14, and 60 days after FMT were examined to evaluate donor phage engraftment. Phages were detected in all sample types, and samples clustered by donation, indicating that the pre-processing steps did not significantly alter the phage profile. The recipients phageome prior to FMT was characterized by low diversity, each recipient being dominated by a different phage. In contrast, the profile 14 days post-FMT demonstrated the engraftment of donor-derived phages, which persisted at 60 days. Most were predicted to be temperate phages of the Caudoviricetes class infecting members of the Clostridia bacterial class, and Lachnospiraceae and Oscillospiraceae bacterial families. Our findings suggest that the CHUV production process for oral FMT capsules preserves the phage community and that donor phages successfully engraft in recipients. Further larger-scale studies and intervention trials will help elucidate the mechanisms underlying the potential of phages in FMTs efficacy.

microbiology↗

Phase Separation and a Hydrodynamic Instability Localize Proteins at Growing Microtubule Ends

Regulating microtubule dynamics is essential for cellular function, and precise localization of regulatory proteins at microtubule ends is critical. End-binding protein EB3, a key regulator of microtubule growth, accumulates over an extended region at the growing end, forming a comet that gradually fragments into transient droplets along the microtubule shaft. Here, we combine in vitro reconstitution experiments with theoretical analysis to show that surface-mediated condensation of EB3 effectively localizes the protein at microtubule ends. Our results reveal that a Rayleigh-Plateau instability limits the condensates extent, producing a finite comet length and discrete droplets along the shaft. Remarkably, the comet size is independent of the GTP-cap size. This finding is supported by experiments on cells showing that modulation of microtubule growth velocity and hence GTP-cap size do not consistently alter EB3 comet length. Furthermore, our theory shows that rapid droplet evaporation requires a transition of EB3 to a non-phase-separating state. Overall, our work challenges the view that comet length directly reflects GTP-cap size and highlights a novel mechanism for regulating microtubule dynamics.

biophysics↗

The effect of motor-induced shaft dynamics on microtubule stability and length

Control of microtubule abundance, stability, and length is crucial to regulate intracellular transport as well as cell polarity and division. How microtubule stability depends on tubulin addition or removal at the dynamic ends is well studied. However, microtubule rescue, the event when a microtubule switches from shrinking to growing, occurs at tubulin exchange sites along the shaft. Molecular motors have recently been shown to promote such exchanges. Using a stochastic theoretical description, we study how microtubule stability and length depends on motor-induced tubulin exchange and thus rescue. Our theoretical description matches our in vitro experiments on microtubule dynamics in presence of kinesin-1 molecular motors. Although the average microtubule dynamics can be captured by an effective rescue rate, the dynamics of individual microtubules differs dramatically when rescue occurs only at exchange sites. Furthermore, we study in detail a transition from bounded to unbounded microtubule growth. Our results provide novel insights into how molecular motors imprint information of microtubule stability on the microtubule network. SIGNIFICANCEThe microtubule network is essential for vital cellular processes like the organization of intracellular transport and division. Although microtubule assembly occurs at its tips, it has recently been reported that tubulin is exchanged along the microtubule shaft. Tubulin exchange plays an essential role in regulating microtubule dynamics and can be induced by molecular motors. Here, we provide the first systematic study of the impact of shaft dynamics on the regulation of rescue events, where a microtubule switches from shrinking to growing. Our results illustrate how the usage of microtubules as tracks for intracellular transport regulates the microtubule network and thus offers a novel perspective on intracellular organization.

biophysics↗