Biology subjects

Ulrich, M.

Publications and source records attributed to Ulrich, M..

6 recordsLinked to original sources

bioRxiv2024

Cell wall arabinogalactan is responsible for Fungitell(R) cross reactivity in nocardiosis

Nocardiosis is a serious infection in immunosuppressed patients, especially transplant recipients. The slow-growing phenotype of the bacterium and the variety of symptoms complicate diagnosis and delay antimicrobial therapy, which results in high mortality rates despite effective treatments. Incidentally, some nocardiosis patients test positive in fungal diagnostics that detect (1,3) {beta}-D-glucan (the Fungitell(R) assay), but the basis for this cross-reactivity remains unknown. We demonstrate that nocardial cell wall arabinogalactan is a cryptic antigen responsible for cross reactivity in the Fungitell(R) assay and that this antigen is revealed in vivo following bacterial cell lysis. We further show that the reactivity results from {beta}-glucose substitution of the galactan domain, a modification specific to Nocardia, and identify the optimal antigen as a tetramer of the trisaccharide repeating unit. By providing structural evidence for Fungitell(R) cross-reactivity during nocardiosis, this work paves the way for developing specific diagnostic tools that are presently lacking.

microbiology↗

bioRxiv2023

Sex differences in anxiety and threat avoidance in GAD65 knock-out mice

Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and the hippocampus, among others. Recent imaging studies suggest sex differences in the activation of this anxiety network during the processing of emotional information. Rodent models with genetically altered {Upsilon}-amino butyric acid (GABA) neurotransmission allow studying the neuronal basis of such activation shifts and their relation to anxiety endophenotypes, but to date sex effects have rarely been addressed. Using mice with a null mutation of the GABA synthetizing enzyme glutamate decarboxylase 65 (GAD65-/-), we started to compare anxiety-like behavior and avoidance in male vs. female GAD65-/- mice and their wildtype littermates. In an open field, female GAD65-/- mice displayed increased activity, while male GAD65-/- mice showed an increased adaptation of anxiety-like behavior over time. GAD65-/- mice of both sexes had a higher preference for social interaction partners, which was further heightened in male mice. In male mice higher escape responses were observed during an active avoidance task. Together, female mice showed more stable emotional responses despite GAD65 deficiency. To gain insights into interneuron function in network structures controlling anxiety and threat perception, fast oscillations (10-45 Hz) were measured in ex vivo slice preparations of the anterior cingulate cortex (ACC). GAD65-/- mice of both sexes displayed increased gamma power in the ACC and a higher density of PV-positive interneurons, which are crucial for generating such rhythmic activity. In addition, GAD65-/- mice had lower numbers of somatostatin-positive interneurons in the basolateral amygdala and in the dorsal dentate gyrus especially in male mice, two key regions important for anxiety and active avoidance responses. Our data suggest sex differences in the configuration of GABAergic interneurons in a cortico-amygdala-hippocampal network controlling network activity patterns, anxiety and threat avoidance behavior. HighlightsO_LIRole of GABA in sex-specific anxiety endophenotypes demonstrated in GAD65-/- mice C_LIO_LISex- and GAD65-dependent alterations in anxiety, social preference and avoidance C_LIO_LIEnhanced in vitro gamma-beta oscillations in ACC slices of GAD65-/- mice C_LIO_LIIncreased parvalbumin(+) interneuron counts in ACC slices of GAD65-/- mice C_LIO_LIReduced somatostatin(+) interneuron counts in dorsal DG and BLA of male GAD65-/- mice C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/532980v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@85ac09org.highwire.dtl.DTLVardef@1e1a70aorg.highwire.dtl.DTLVardef@19dbbeforg.highwire.dtl.DTLVardef@9d52ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Comparative metagenomics reveals host-specific functional adaptation of intestinal microbiota across hominids

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we performed high-resolution metagenomic-based analyses of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in humans populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer new and exciting insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids, demonstrating that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.

evolutionary biology↗

bioRxiv2020

Leprosy in wild chimpanzees

Humans are considered the main host for Mycobacterium leprae, the aetiologic agent of leprosy, but spill-over to other mammals such as nine-banded armadillos and red squirrels occurs. Although naturally acquired leprosy has also been described in captive nonhuman primates, the exact origins of infection remain unclear. Here, we report on leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in the Cantanhez National Park, Guinea-Bissau, and the Tai National Park, Cote dIvoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). The independent evolutionary origin of M. leprae in two geographically distant populations of wild chimpanzees, with no prolonged direct contact with humans, suggests multiple introductions of M. leprae from an unknown animal or environmental source.

evolutionary biology↗

bioRxiv2019

The history of measles: from a 1912 genome to an antique origin

Many infectious diseases are thought to have emerged in humans after the Neolithic revolution. While it is broadly accepted that this also applies to measles, the exact date of emergence for this disease is controversial. Here, we sequenced the genome of a 1912 measles virus and used selection-aware molecular clock modeling to determine the divergence date of measles virus and rinderpest virus. This divergence date represents the earliest possible date for the establishment of measles in human populations. Our analyses show that the measles virus potentially arose as early as the 4th century BCE, rekindling the recently challenged hypothesis of an antique origin of this disease. One Sentence SummaryMeasles virus diverged from rinderpest virus in the 4th century BCE, which is compatible with an emergence of measles during Antiquity.

evolutionary biology↗

bioRxiv2019

Geographically structured genomic diversity of non-human primate-infecting Treponema pallidum subsp. pertenue

BackgroundIncreasing evidence suggests many non-human primate (NHP) species in sub-Saharan Africa are infected with Treponema pallidum subsp. pertenue (TPE), the bacterium causing yaws in humans. In humans, yaws is characterized by lesions of the extremities and face, while Treponema pallidum subsp. pallidum (TPA) causes venereal syphilis and is characterized by primary lesions on the genital, anal or oral mucosae, and has not been detected in NHPs. Due to a paucity of genetic data, it remains unclear whether other Treponema pallidum (TP) subspecies found in humans also occur in NHP and how the genomic diversity of TPE lineages that do occur in NHPs is distributed across hosts and space. MethodologyWe observed a combination of yaws- and syphilis-like symptoms in sooty mangabeys (Cercocebus atys atys) in Tai National Park (TNP), Cote dIvoire and collected swabs and biopsies from symptomatic animals. We also collected NHP bones from eight species from TNP, as well as from 19 species at 12 field sites across sub-Saharan Africa. Samples were screened for TP DNA using PCRs. In-solution hybridization capture coupled with high throughput sequencing was used to sequence TP genomes from positive samples. Principal findingsWe generated four nearly complete TP genomes from biopsies and swabs and five partial genomes from bones. Phylogenomic analyses revealed that both syphilis- and yaws-like lesions of sooty mangabeys within a single social group in TNP were caused by TPE. All TPE genomes determined from these sooty mangabeys were different and exhibited divergence levels not observed in TPE from a single species at any other field site where the disease seems to be epizootic. In general, simian TPE isolates did not form monophyletic clades based on host species or the type of symptoms caused by an isolate, but rather clustered based on geography. ConclusionsThere is a large diversity of TPE strains infecting NHPs in TNP. Our observations within a single social group of sooty mangabeys do not support the epizootic spread of a single clone, but rather points towards frequent independent introductions of the bacterium, which can cause syphilis- and yaws-like lesions. On a larger scale, the geographic clustering of TPE genomes might be compatible with cross-species transmission of TPE within ecosystems or environmental exposure leading to acquisition of closely related strains. Authors summaryIndividuals in several populations of wild non-human primates (NHP) in sub-Saharan Africa are infected with Treponema pallidum subsp. pertenue (TPE), a pathogen causing yaws disease in humans. In humans, yaws is characterized by skin lesions of the extremities and face. In contrast, Treponema pallidum subsp. pallidum, which causes venereal syphilis in humans, has not been observed in NHPs. We describe a combination of yaws- and syphilis-like symptoms in a sooty mangabey (Cercocebus atys atys) social group in Tai National Park (TNP), Cote dIvoire. We sampled lesioned animals and collected and tested NHP bones from field sites across sub-Saharan Africa. We were able to reconstruct four genomes from swabs/biopsies and five partial genomes from bone samples. Phylogenomic analyses revealed that syphilis-like lesions and yaws-like lesions in TNP were caused by a large diversity of TPE strains. Additionally, simian TPE isolates did not form monophyletic clades based on the host species or the types of symptoms caused by an isolate, but rather clustered by geographic origin. This is suggestive of cross-species transmission of TPE within ecosystems or environmental exposure leading to acquisition of closely related strains.

genomics↗