Ontogenetic and geographic venom variation in the Great Basin Rattlesnake, Crotalus oreganus lutosus

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  Ontogenetic and geographic venom variation in the Great Basin Rattlesnake, Crotalus oreganus lutosus Abstract Venom composition among the species of the Western Rattlesnake clade is often quite variable, depending on several factors such as geographic location and ontogeny. Venom composition not only affects the ability of a snake to acquire prey efficiently, but it can also significantly impact snakebite symptomology. Currently, there has been limited characterization of the venom from the Great Basin Rattlesnake ( Crotalus oreganus lutosus ), a lineage that is broadly distributed in the intermontane western United States. In this study we sample 67 individual Great Basin Rattlesnakes collected in Idaho, Utah, California, and Arizona. We find evidence for substantial ontogenetic and geographic variation in venom composition. Of the six toxin families assessed, all showed ontogenetic shifts to varying extents, with some trends differing from those observed in other rattlesnake sp...

Engineered Bacteria-Mediated Delivery of Scorpion Venom Peptide AGAP for Targeted Breast Cancer Therapy

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Engineered Bacteria-Mediated Delivery of Scorpion Venom Peptide AGAP for Targeted Breast Cancer Therapy

Abstract

The rising incidence and mortality rates of malignant tumors highlight their profound impact on human health. Bacterial therapy has emerged as a promising avenue in oncological research. Our lab has isolated an analgesic-anti-tumor peptide from the venom of Buthus martensii Karsch (BmK AGAP), a long-chain scorpion venom peptide, which exhibits remarkable anti-tumor activity. However, the limited bioavailability of peptides poses a challenge for their therapeutic efficacy. To address this challenge, we focused on enhancing the delivery of BmK AGAP to improve its anti-tumor effectiveness. We engineered E. coli K12 to create the TSYPU strain, which not only expresses BmK AGAP, but also possesses lytic capabilities. Co-culturing of TSYPU with murine breast cancer 4T1 cells in vitro demonstrated its potential as a drug delivery platform. Further advancements included the encapsulation of TSYPU with nanogold particles, resulting in TSYPU@Au strain. In vivo experiments revealed that TSYPU@Au exhibited a significant anti-tumor effect, crucially overcoming degradation in the acidic gastrointestinal environment. In summary, our study highlights the viability of engineered TSYPU bacteria as carriers for BmK AGAP delivery, offering a promising approach for the rational design of bacterial-based peptide drug delivery systems in oncology. This strategy has considerable potential for advancing the field and warrants further investigation in future studies.

Zhang, Y., Li, X., Tian, C. et al. Engineered Bacteria-Mediated Delivery of Scorpion Venom Peptide AGAP for Targeted Breast Cancer Therapy. Curr Microbiol 82, 323 (2025). https://doi.org/10.1007/s00284-025-04289-9