Biology subjects

Schneeberger, P. H. H.

Publications and source records attributed to Schneeberger, P. H. H..

7 recordsLinked to original sources

bioRxiv2026

The antiparasitics ivermectin and moxidectin trigger genomic and transcriptomic adaptation in bacteria

The macrocyclic lactone anthelmintics ivermectin and moxidectin are widely used for parasite control and show antibacterial activity in vitro. Given their structural relatedness to macrolide antibiotics, their broad use raises concerns about macrolide cross-resistance and altered bacterial physiology, yet the impact on gut bacterial isolates and underlying mechanisms remains poorly defined. Here, we combined Oxford Nanopore whole genome sequencing with Illumina RNA sequencing across six bacterial isolates analyzed as unexposed controls and as derivatives repeatedly exposed to ivermectin or moxidectin to identify genomic and transcriptomic signatures associated with exposure to these drugs. High-quality genome assemblies enabled integrated analyses across species with distinct cellular architectures and antimicrobial resistance gene arsenals. Across the panel, exposure was associated with i) widespread modulation of ribosome-linked genes and pathways, the molecular target of macrolide antibiotics; ii) context-dependent tuning of pre-existing antimicrobial resistance gene arsenals, such as macB and mdlB; and iii) recurrent alterations in potassium transport systems (ktrA and trkA). These findings suggest that repeated ivermectin or moxidectin exposure can reshape bacterial physiology in ways that may, in specific genetic backgrounds, co-modulate resistance-associated traits.

microbiology↗

bioRxiv2025

Hybrid-metagenomics reveal off-target effects of albendazole, ivermectin-albendazole and moxidectin-albendazole on the human gut bacteria.

The human whipworm parasite, Trichuris trichiura, poses a critical public health problem, affecting over 400 million people globally and responding poorly to the standard-of-care - benzimidazole chemotherapy. Recent efforts aimed at developing improved treatment options, the two macrolide-benzimidazole combination therapies ivermectin-albendazole and moxidectin-albendazole. Recent reports suggest that ivermectin and moxidectin possess antibacterial properties in vitro, hence there is a need to comprehensively characterize their off-target effects on the gut microbiome. In the framework of a randomized-controlled trial we collected stool samples of 204 T. trichiura-infected individuals in Cote dIvoire receiving albendazole (400mg), albendazole-ivermectin (400mg/200{micro}g/kg) and albendazole-moxidectin (400mg/8mg). Using a state-of-the-art hybrid sequencing approach that combines Illumina short read and Oxford Nanopore long read shotgun sequencing, we recovered over 800 high-quality metagenome-assembled genomes. Our analyses reveal that albendazole and albendazole-moxidectin induce taxonomic shifts in the gut microbiota with only mild functional consequences. In contrast, in individuals receiving higher quantities of albendazole-ivermectin (ivermectin > 12mg), based on their weight, we observed profoundly modulated taxonomic composition and microbial function, while the resistome was largely spared. These findings robustly confirm ivermectins antibacterial properties in the human gut, extending beyond previously reported in vitro effects. Given that ivermectin is a cornerstone in parasitic disease control, it is crucial to evaluate its broader impacts and considering more targeted, evidence-based treatment strategies.

genomics↗

bioRxiv2025

Profound taxonomic and functional gut microbiota alterations associated with trichuriasis: cross-country and country-specific patterns

BackgroundThe human gastrointestinal microbiota plays a crucial role in immune modulation, metabolism, and pathogen resistance. Soil-transmitted helminth (STH) infections, including Trichuris trichiura (whipworm), significantly alter gut microbial composition, yet the extent and functional consequences of these changes remain underexplored across different geographical regions. This study investigates the taxonomic and functional impacts of T. trichiura on gut microbiota in three endemic regions - Cote dIvoire, Laos, and Tanzania - using a unified high-resolution metagenomic sequencing approach. ResultsThis study reveals extensive gut microbiota disruptions linked to T. trichiura infection, with both regional and cross-country patterns. A core signature found across all study sites includes depletion of Faecalibacterium prausnitzii and Eubacterium rectale (Short-chain fatty acids (SCFA) producers) and enrichment of mucin-degrading bacteria (Ruminococcus, Bacteroides), alongside increased host-derived carbohydrate metabolism. Infection destabilized microbial networks, characterized by reduced connectivity and clustering, with opportunistic taxa such as Segatella copri emerging as network hubs across regions, indicating a shared ecological response. Both taxonomic and functional disruptions exhibited a combination of conserved and region-specific patterns; for example, whereas certain taxa, such as Prevotella and Streptococcus, showed notable geographic variability, specific functional changes, such as SCFA depletion and mucin degradation, were consistently observed across sites. These conserved functional changes suggest that T. trichiura imposes similar metabolic pressures on the gut microbiome across populations, potentially affecting host nutrient availability and immune responses in a predictable manner. Discussion and ConclusionThis study provides robust evidence that T. trichiura infection induces significant and consistent microbiome alterations across diverse populations. The depletion of SCFA-producing bacteria and the enrichment of mucin-degrading taxa, along with corresponding metabolic pathways, imply compromised gut barrier integrity, providing insights into the complex inflammatory processes associated with this helminth infection. Additionally, these microbiome differences could play a critical role in facilitating parasite persistence and reinfection, which remain major challenges limiting the efficacy of global control strategies. Our findings highlight the potential of microbiome-targeted interventions, such as probiotic supplementation or dietary modifications, to mitigate the health impacts of T. trichiura infections by restoring microbial homeostasis.

microbiology↗

bioRxiv2024

Nanopore-based analysis unravels the genetic landscape and phylogenetic placement of human-infecting Trichuris species in Cote d'Ivoire, Tanzania, Uganda, and Laos

Soil-transmitted helminthiases, particularly trichuriasis, affect over 500 million people, mostly in low- and middle-income countries. Traditional diagnostics fail to distinguish between Trichuris species, obscuring transmission patterns and treatment outcomes. Using nanopore-based full-length ITS2 rDNA sequencing, we analyzed 687 samples from Cote dIvoire, Laos, Tanzania, and Uganda, confirming the phylogenetic placement of Trichuris trichiura and the recently described Trichuris incognita. We identified two genetically distinct Trichuris species infecting humans, with divergent geographic patterns and presence in non-human primates, suggesting complex host-parasite dynamics. Within-country genetic variation indicated local adaptation and cryptic population structure. Importantly, we demonstrated that ITS2 fragment length is a robust, cost-effective diagnostic marker for differentiating T. incognita and T. trichiura, offering a practical alternative to sequencing for resource-limited settings. These findings expose the hidden complexity of Trichuris infections and highlight the urgent need to update diagnostic and control strategies to account for overlooked species diversity in endemic regions.

genomics↗

bioRxiv2024

Genetic makeup of Trichuris hominibus, a novel Trichuris species naturally infecting humans and displaying signs of resistance to drug treatment

BackgroundTrichuriasis is a neglected tropical disease that affects as many as 500 million individuals and can cause significant morbidity. For decades, it was thought to be caused by one species of whipworm, Trichuris trichiura. Significant differences in response rates to the best available anthelmintic treatment for trichuriasis -- a combination of albendazole and ivermectin -- exist across clinical trial reports yet the underlying reasons are unclear. MethodsCombining long- and short- read sequencing approaches, we assembled a high- quality reference genome of T. incognita n. sp. isolated in an interventional study conducted in Cote dIvoire. The species tree of the Trichuris genus was constructed using 12434 orthologous groups. We sequenced a total of 747 individual worms which were used to confirm the phylogenetic placement and investigate patterns of adaptation through comparative genomic analysis. FindingsHere, we present and characterize a human-infecting Trichuris species that we named Trichuris incognita n. sp. Comparative genomic analysis of genes suspected to confer resistance to either albendazole or ivermectin in helminths revealed a high number of beta- tubulin (TBB) orthologs, present in the whole population of T. incognita n. sp., compared to the canonical T. trichiura species, but these genes were not associated to a resistant phenotype. We conducted a genome wide association study (GWAS) comparing 179 albendazole-ivermectin sensitive to 542 drug non-sensitive worms, which did not conclusively show an adaptation to drug pressure within the same species. InterpretationOur results demonstrate that trichuriasis can be caused by multiple species of whipworm and that the differences in response rates, may be a result of species responding differently to drug treatment, as opposed to an establishment of resistance. This discovery, coupled with the high tolerability of T. incognita n. sp. to albendazole-ivermectin marks a significant shift in how we understand and approach whipworm infections. FundingEuropean Research Council (ERC) Nr. 101019223. Research in context Panel: Evidence before this studyThe recommended treatment with the benzimidazoles albendazole or mebendazole shows consistently low efficacy against T. trichiura, and therefore combination chemotherapy of benzimidazoles and ivermectin has been recommended. Recent clinical trials with albendazole-ivermectin, showed especially low cure rates against what was presumed to be T. trichiura in Cote dIvoire, in contrast to higher efficacy observed in Laos and Pemba, Tanzania. Amplicon sequencing data pointed towards underlying genomic differences and potentially a new species of human infecting Trichuris in Cote dIvoire. Added value of this studyWe identified and described a morphologically indistinguishable, novel causative agent of trichuriasis that doesnt respond to conventional drug treatment: Trichuris incognita n. sp. We provide a high-quality reference genome of this novel species and sequencing data of 747 individual isolates. A genome wide association study did not conclusively show adaptation to drug pressure. This study demonstrates that trichuriasis can be caused by multiple species of whipworm and that the differences in response rates, may be a result of species responding differently to drug treatment, as opposed to an establishment of resistance. Implications of all the available evidenceThe current whole body of evidence calls for new effective treatments against T. incognita n. sp. Due to the morphological indistinguishableness, molecular diagnostic tools need to be implemented to identify species level differences as opposed to the traditional Kato Katz method. The geographical distribution of T. incognita as well as longitudinal changes of species distributions will need to be mapped, in addition to better understanding of the new species pathology and transmission dynamics.

genomics↗

bioRxiv2021

Performance characteristics of next-generation sequencing for antimicrobial resistance gene detection in genomes and metagenomes

Short-read sequencing provides a culture-independent method for the detection of antimicrobial resistance (AMR) genes from single bacterial genomes and metagenomic samples. However, the performance characteristics of these approaches have not been systematically characterized. We compared assembly- and read-based approaches to determine sensitivity, positive predictive value, and sequencing limits of detection required for AMR gene detection in an Escherichia coli ST38 isolate spiked into a synthetic microbial community at varying abundances. Using an assembly-based method the limit of detection was 15X genome coverage. We are confident in AMR gene detection at target relative abundances of 100% to 1%, where a target abundance of 1% would require assembly of approximately 30 million reads to achieve 15X target coverage. Recent studies assessing AMR gene content in metagenomic samples may be inadequately sequenced to achieve high sensitivity. Our study informs future sequencing projects and analytical strategies for genomic and metagenomic AMR gene detection.

bioinformatics↗

bioRxiv2020

Two-target quantitative PCR to predict library composition for shallow shotgun sequencing

Shotgun sequencing enables retrieving high resolution information 40 from complex microbial communities. However, the technique is limited by missing information about host-to-microbe ratios observed in different sample types. This makes it challenging to plan sequencing experiments, especially in the context of high sample multiplexing and/or limited sequencing output. We evaluated a qPCR-based assay to predict host-to microbe ratio prior to sequencing. Using a two-target assay aimed at conserved human and bacterial genes, we predicted human-to-microbe ratios in two sample types and validated it on independently collected samples. The assay enabled accurate prediction for a broad range of sample compositions.

microbiology↗