Biology subjects

Lueddecke, T.

Publications and source records attributed to Lueddecke, T..

12 recordsLinked to original sources

bioRxiv2026

Ontogenetic variation in composition and bioactivity of common adder (Vipera berus) venom revealed by genome-guided proteomics and in vitro functional assays

1Ontogenetic shifts in diet are well documented in snakes and are increasingly linked to age-related venom variation. The common adder, Vipera berus, exhibits a dietary transition from predominantly ectothermic prey in its early life to increasingly incorporating endothermic prey as an adult. Here, we investigate whether this dietary shift is reflected in age-related changes in the venom composition and bioactivity of V. berus. Venoms from captive-bred V. berus from Germany were obtained and pooled across five age groups, from neonates to adults. Venom profiles were assessed by SDS-PAGE and genome-guided shotgun proteomics, with quantification based on normalized spectral abundance factors (NSAF) using a toxin-gene catalogue generated from a novel V. berus genome assembly. In parallel, we assayed general protease and PLA2 activities, as well as FXa-, thrombin-, and plasmin-like activities, and cytotoxicity toward mammalian cell lines. We identified two distinct age-related venom phenotypes (ontotypes): an svMP/CTL-rich ontotype A ([≤]1 year) and an svSP/PLA2-rich ontotype B ([≥]2 years). Functionally, protease activity decreased with age, whereas thrombin-like, plasmin-like and PLA2 activities, and cytotoxicity, increased. Our findings indicate an ontogenetic shift in composition and activities of V. berus venom that parallels dietary transitions and potentially reflect adaptation to differing prey physiologies.

biochemistry↗

bioRxiv2025

Transcriptomic assessment of the Black Judaicus scorpion (Hottentotta judaicus) toxin arsenal and its potential bioeconomic value

Scorpion venoms are likewise a medical burden as well as a source of novel bioresources. Despite their important dual role, the venoms of most scorpion species remain under- or unstudied. Among these is the venom of the Black Judaicus scorpion, Hottentotta judaicus (Simon, 1872), a common yet neglected species native to the Middle East. Here, we employ venom gland transcriptomics to investigate its toxin-encoding precursor profile to gain insight into its toxin repertoire. The venom was found to be composed primarily of various short scorpion toxins, long scorpion toxins from the 3 C-C as well as the 4 C-C type, and enzymatic components. Minor components include, defensins and putative antimicrobial peptides. Several identified toxins show similarity to known neurotoxins from lethal buthids or to toxins with translational value in biomedicine, agriculture, and industrial production, thus rendering H. judaicus both, a potential health concern and source of novel bioresources. Our work provides an extended perspective on the venom profile of this species and represents a basis for future follow-up studies.

zoology↗

bioRxiv2025

Venomous Maggots? A first exploration of the toxin arsenal of larval stages of the horse fly Tabanus autumnalis

As a rapidly evolving trait, animal venom exhibits compositional variation even at the intraspecific level between populations, ontogenetic stages and sexes. In extreme cases venom is used for different functional purposes across ontogenetic stages. This phenomenon occurs for example in case of horse flies (Tabanidae), which utilize venom for predation during the larval stage and for blood feeding in the adult stage. While the venom composition and activity of adult tabanids has been investigated for some species, nothing is known about the venom compounds of tabanid larvae. With the current study we provide first insights into the venom composition of larval stages of a tabanid. Besides a plethora of hydrolyzing enzymes, we find the venom of T. autumnalis larvae dominated by peptide toxins. Some of these peptide toxins could be annotated as putative neurotoxins and cytolytic peptides and these compounds likely are the main drivers of fast prey incapacitation. Previous studies identified the main functional constituents utilized by tabanid imagines for blood feeding to be protease inhibitors affecting vasoconstriction and thrombin to promote blood feeding. Interestingly we find highly similar putative protease inhibitors in the larval venom, though with relatively low expression levels. This provides a first indication for a shifted expression profile between the venom of tabanid life stages to fulfill both the predatory needs of the larvae and the blood lust of female imagines.

molecular biology↗

bioRxiv2025

A genome-guided atlas to the composition, activity, and β-bungarotoxin dimerization in many-banded krait venom inferred by functional venomics

1Snakebite is a neglected tropical disease claiming [~]140,000 lives every year. One of the most medically relevant snakes of Asia is the many-banded krait (Bungarus multicinctus). Approximately 8% of the global human population is at risk of being envenomated by this species, able to cause fatal neurotoxicity. Here, we present a proteogenomic and functional assessment of the B. multicinctus venom via genome-guided bottom-up and top-down proteomics, combined with traditional protein profiling and bioassays. We report its venom profile alongside the primary structures of its toxins, revealing a relatively simple venom containing 55 components from 16 protein families. It is largely composed by three-finger toxins and phospholipase A2, besides acetylcholinesterase and snake venom metalloprotease. Top-down data unveiled the diversity of the highly lethal {beta}-bungarotoxins and allowed us to infer the complex dimerization patterning of these multi-domain neurotoxins. Our functional analysis revealed that B. multicinctus venom exerts potent phospholipase A2 and acetylcholinesterase activities, but protease activity as well as effects on cell viability and release of second messengers were virtually absent. This suggests, that B. multicinctus venom causes its devastating neurotoxic symptoms due to a heavy reliance on phospholipase A2 and acetylcholinesterase, but without impairing viability of neurons nor via interference of second messenger release. Antibacterial and antiviral screens further revealed activity against some pathogenic microbes that warrant further translational investigations. A comparison to previously published venom proteomes of B. multicinctus and its congeners suggests, that intraspecific venom variation occurs more widely in kraits than previously acknowledged and deserves higher attention. Overall, our investigation provides pivotal new insights into the biochemistry and pathophysiology of one of earths most lethal snakes and represents an important resource to inform future proteogenomic and functional studies in krait venom and beyond.

molecular biology↗

bioRxiv2025

Convergent evolutionary adaption of spider venom from predation to defense

Most spiders deploy paralytic venom for prey capture, but adults of the yellow-sac spider (Cheiracanthium punctorium) instead produce a predominantly defensive venom to safeguard their offspring. Here, we characterized the molecular repertoire of C. punctorium venom to shed light on its evolutionary history. Unlike venom in other spiders, C. punctorium venom mostly comprises neurotoxic double-domain neurotoxin 19 family (CSTX) peptides and enzymes, such as phospholipase A2 (PLA2). Comparative venomics in four spiders representing two infraorders showed that CSTXs arose following the mygalomorph- araneomorph split [~]300 mya by means of ancestral gene duplication and functional specialization. A gene fusion event then merged CSTXs from two distinct clades to form the double-domain toxin. PLA2 proteins were convergently recruited to C. punctorium to fulfil a defensive function and are strikingly similar to proalgesic PLA2 proteins in bee venom. These complex, multimodal molecular innovations in venom systems highlight natures tendency to use the same molecular solutions for similar ecological challenges across diverse animal lineages.

zoology↗

bioRxiv2024

Comparative venom analysis between melanistic and normally-colored phenotypes of the common adder (Vipera berus)

1Snake venom is an ecologically-relevant functional trait directly linked with a snakes fitness and survival, facilitating predation and defense. Snake venom variation occurs at all taxonomic levels, but the study of variation at intraspecific level is still in its early stages. The common adder (Vipera berus) exhibits considerable variation in color phenotypes across its distribution range. Melanistic (fully black) individuals are the subject of myths and fairytales, and in German folklore such "hell adders" are considered more toxic than their normally-colored conspecifics. However, these claims have never been formally tested. Here, we provide the first comparative analysis of venoms from melanistic and normally-colored common adders. Specifically, we compared the venom profiles by SDS-PAGE and RP-HPLC, and tested the protease, phospholipase A2 and cytotoxic activities of the venoms of both phenotypes. Phospholipase A2 activity was similar in both phenotypes, whereas general protease activity was higher in the melanistic venom, which was also more cytotoxic at two concentrations (6.25 and 12.5 {micro}g/ml). These minor differences between the venoms of melanistic and normally-colored adders are unlikely to be of clinical relevance in the context of human envenomation. In light of our results, the claim that melanistic adders produce more toxic venom than their normally-colored conspecifics appears rooted entirely in folklore.

molecular biology↗

bioRxiv2024

Engineering a wolf spider A-family toxin towards increased antimicrobial activity but low toxicity

Peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.

bioengineering↗

bioRxiv2024

Enlighting the toxinological dark matter of spider venom enzymes

Spiders produce highly adapted venoms featuring a complex mixture of biomolecules used mainly for hunting and defense. The most prominent components are peptidic neurotoxins, which have been the focus of research and drug development, whereas venom enzymes have been largely neglected. Nevertheless, investigation of venom enzymes not only reveals insights into their biological functions, but also provides templates for future industrial applications. Here we compared spider venom enzymes contained in the VenomZone database and in other publicly available proteo-transcriptomic datasets. We found extensive discrepancies between these sources, revealing a previously unrecognized abundance and diversity of venom enzymes. Furthermore, we assigned the reported enzymes to cellular processes and known venom functions, including toxicity, prey pre-digestion, venom preservation, venom component activation, and venom spreading factors. Our study reveals a gap between databases and publications in terms of enzyme coverage which impedes development of new applications based on the rich and diverse spectrum of enzymes contained in spider venom.

biochemistry↗

bioRxiv2022

Large-scale unsupervised discovery of excitatory morphological cell types in mouse visual cortex

Neurons in the neocortex exhibit astonishing morphological diversity which is critical for properly wiring neural circuits and giving neurons their functional properties. However, the organizational principles underlying this morphological diversity remain an open question. Here, we took a data-driven approach using graph-based machine learning methods to obtain a low-dimensional morphological "bar code" describing more than 30,000 excitatory neurons in mouse visual areas V1, AL and RL that were reconstructed from the millimeter scale MICrONS serial-section electron microscopy volume. Contrary to previous classifications into discrete morphological types (m-types), our data-driven approach suggests that the morphological landscape of cortical excitatory neurons is better described as a continuum, with a few notable exceptions in layers 5 and 6. Dendritic morphologies in layers 2-3 exhibited a trend towards a decreasing width of the dendritic arbor and a smaller tuft with increasing cortical depth. Inter-area differences were most evident in layer 4, where V1 contained more atufted neurons than higher visual areas. Moreover, we discovered neurons in V1 on the border to layer 5 which avoided deeper layers with their dendrites. In summary, we suggest that excitatory neurons morphological diversity is better understood by considering axes of variation than using distinct m-types.

neuroscience↗

bioRxiv2022

TMPRSS2 is essential for SARS-CoV-2 Beta and Omicron infection

The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts whether TMPRSS2 inhibitors would be suitable for treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to spread of SARS-CoV-2 in the infected host is largely unclear. Here, we show that loss of TMPRSS2 strongly reduced the replication of the Beta variant in nose, trachea and lung of C57BL mice and protected the animals from weight loss and disease. Infection of mice with the Omicron variant did not cause disease, as expected, but again TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify a key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection and highlight TMPRSS2 as an attractive target for antiviral intervention.

immunology↗

bioRxiv2020

An economic dilemma between weapon systems may explain an arachno-atypical venom in wasp spiders (Argiope bruennichi)

Spiders use venom to subdue their prey, but little is known about the diversity of venoms in different spider families. Given the limited data available for orb-weaver spiders (Araneidae) we selected the wasp spider Argiope bruennichi for detailed analysis. Our strategy combined a transcriptomics pipeline based on multiple assemblies with a dual proteomics workflow involving parallel mass spectrometry techniques and electrophoretic profiling. We found that the remarkably simple venom of A. bruennichi has an atypical composition compared to other spider venoms, prominently featuring members of the CAP superfamily and other, mostly high-molecular-weight proteins. We also detected a subset of potentially novel toxins similar to neuropeptides. We discuss the potential function of these proteins in the context of the unique hunting behavior of wasp spiders, which rely mostly on silk to trap their prey. We propose that the simplicity of the venom evolved to solve an economic dilemma between two competing yet metabolically expensive weapon systems. This study emphasizes the importance of cutting-edge methods to encompass smaller lineages of venomous species that have yet to be characterized in detail, allowing us to understand the biology of their venom systems and to mine this prolific resource for translational research.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗

bioRxiv2018

Tarantula phylogenomics: A robust phylogeny of multiple tarantula lineages inferred from transcriptome data sheds light on the prickly issue of urticating setae evolution

Mygalomorph spiders of the family Theraphosidae, known to the broader public as tarantulas, are among the most recognizable arachnids on earth due to their large size and widespread distribution. Their use of urticating setae is a notable adaptation that has evolved exclusively in certain New World theraphosids. Thus far, the evolutionary history of Theraphosidae remains poorly understood; theraphosid systematics still largely relies on morphological datasets, which suffer from high degrees of homoplasy, and traditional targeted sequencing of preselected genes failed to provide strong support for supra-generic clades (i.e. particularly those broader than subfamilies). In this study, we provide the first robust phylogenetic hypothesis of theraphosid evolution inferred from transcriptome data. A core ortholog approach was used to generate a phylogeny from 2460 orthologous genes across 25 theraphosid genera, representing all of the major theraphosid subfamilies, except Selenogyrinae. For the first time our phylogeny recovers a monophyletic group that comprises the vast majority of New World theraphosid subfamilies including Aviculariinae and Theraphosinae. Concurrently, we provide additional evidence for the integrity of questionable subfamilies, such as Poecilotheriinae and Psalmopoeinae, and support the non-monophyly of Ischnocolinae. The deeper relationships between almost all subfamilies are confidently inferred for the first time. We also used our phylogeny in tandem with published morphological data to perform ancestral state analyses on urticating setae. This revealed that the evolution of this important defensive trait might be explained by three equally parsimonious scenarios.

evolutionary biology↗