Biology subjects

Dersch, L.

Publications and source records attributed to Dersch, L..

3 recordsLinked to original sources

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↗

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↗