Functional characterization of antimicrobial peptides from the venom of the scorpion Chihuahuanus coahuilae

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Functional characterization of antimicrobial peptides from the venom of the scorpion Chihuahuanus coahuilae

Abstract

Background: Antibiotic resistance is a major global health challenge driven by the declining availability of effective antimicrobials. Antimicrobial peptides (AMPs) from venomous organisms are promising alternatives because of their broad-spectrum activity and low propensity for resistance development. Chihuahuanus coahuilae, an endemic scorpion from northern Mexico, produces a venom rich in bioactive peptides with potential therapeutic applications.

Methods: Venom gland transcriptomic analysis identified four novel AMP sequences, which were chemically synthesized and evaluated through structural, antimicrobial, hemolytic, cytotoxicity, and immunological assays. Antibacterial activity was assessed against clinically relevant bacterial strains, including a multidrug-resistant Acinetobacter baumannii isolate. Hemolysis was evaluated using human erythrocytes, and immunocompatibility was determined in peripheral blood mononuclear cells (PBMCs) by measuring T-cell viability and cytokine production.

Results: The peptides exhibited bactericidal activity against Enterococcus faecalis (EC50 = 86.5-157.3 µM), Escherichia coli (EC50 = 22.7-69.6 µM), and multidrug resistant A. baumannii (EC50 = 11.4-97.7 µM). Hemolytic activity remained below 10% at concentrations up to 20 µM. T-cell viability exceeded 85% at antimicrobial EC50 concentrations, indicating limited cytotoxicity. Cytokine profiling revealed no significant induction of TNF-α or IL-6 at therapeutically relevant concentrations, supporting a favorable immunocompatibility profile.

Conclusion: These findings identify four novel venom-derived AMPs with potent antibacterial activity, low hemolytic and cytotoxic effects, and minimal immunostimulatory properties. Their combined antimicrobial efficacy and favorable safety profile support further preclinical development as candidates for treating multidrug-resistant bacterial infections.


Alvarado-González, C., Beltran, L. F. L.-A., Clement, H., Gastelum-Arellanez, A., Camacho-Silvas, L. A., Hinojos-Gallardo, L. C., Peralta-Pérez, M. del R., Ballinas-Casarrubias, L., Corzo, G., & Espino-Solis, G. P. (2026). Functional characterization of antimicrobial peptides from the venom of the scorpion Chihuahuanus coahuilae. Journal of Venomous Animals and Toxins Including Tropical Diseases, 32, e20260021. https://doi.org/10.1590/1678-9199-JVATITD-2026-0021