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From Venom to Veterinary Therapeutics: Snake Venom-Derived Molecules Against Antimicrobial-Resistant Bacteria in the One Health Era

Submitted:

11 August 2026

Posted:

12 August 2026

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Abstract
Antimicrobial resistance (AMR) is one of the most significant challenges facing human and veterinary medicine today. It reduces the effectiveness of conventional antibiotics against multidrug-resistant (MDR) pathogens. Snake venoms are complex mixtures of proteins, peptides, and enzymes that have evolved to target biological membranes and cellular processes. Over the past decade, numerous molecules derived from snake venom have shown promising antibacterial and antibiofilm activity against clinically relevant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and resistant Escherichia coli. Among the most promising compounds are phospholipases A₂ (PLA₂s), L-amino acid oxidases (LAAOs), cathelicidins, crotalicidin-derived peptides, and synthetic peptides engineered from natural venom sequences. Their antimicrobial activity primarily acts through mechanisms such as membrane disruption, induction of oxidative stress, inhibition of biofilm formation, and synergistic interactions with conventional antibiotics. However, native venom toxins often exhibit cytotoxicity, haemolytic activity, and poor pharmacokinetic properties, limiting their direct clinical application. Therefore, current research focuses on rational peptide engineering, nanotechnology-based delivery systems, and combination therapies to enhance efficacy while minimising toxicity. This mini-review summarises recent advances in snake venom-derived antimicrobial molecules, discusses their potential applications in veterinary medicine, and emphasises their importance within the One Health framework.
Keywords: 
antimicrobial resistance
;  
One Health
;  
snake venom
;  
veterinary medicine
Subject: 
Biology and Life Sciences  -   Other

Introduction

Antimicrobial resistance (AMR) has emerged as a critical challenge to both global public health and veterinary medicine, posing a growing threat that undermines the efficacy of established antimicrobial agents. The World Health Organisation (WHO) has highlighted AMR as one of the top 10 global public health threats facing humanity, as it compromises the treatment of infectious diseases and contributes to prolonged illness, increased healthcare costs, and heightened mortality rates (WHO, 2023; 2024).
Increasing instances of multidrug-resistant (MDR) bacteria have been documented across species, including companion animals, livestock, wildlife, and human populations. The spread of resistance genes has significantly reduced the effectiveness of standard therapeutic regimens, posing substantial challenges for clinicians and veterinarians (Brown et al., 2019; Laxminarayan et al., 2013). Notable pathogens contributing to this crisis include methicillin-resistant Staphylococcus aureus (MRSA), prevalent in both hospital and community settings, and methicillin-resistant Staphylococcus pseudintermedius (MRSP), frequently isolated from companion animals (Cai et al., 2018; Nocera et al., 2024; Stefanetti et al., 2024).
Additionally, pathogens such as carbapenem-resistant Acinetobacter baumannii and multidrug-resistant Pseudomonas aeruginosa exhibit remarkable resilience against conventional antibiotics, posing significant treatment challenges in clinical settings (Nguyen et al., 2021; Shao et al., 2020). Extended-spectrum β-lactamase (ESBL)- producing Enterobacterales, which are increasingly found in both human and veterinary medicine, further complicate infection management and underscore the urgent need for robust surveillance and intervention strategies (Zhang et al., 2025).
Addressing the threat of AMR necessitates coordinated efforts across sectors, including the prudent use of antimicrobials, enhanced infection prevention and control practices, and ongoing research into novel therapeutic options (Oleveira et al., 2024).
Natural toxins are attracting growing interest as sources of new antimicrobial agents (Muttiah and Hanafiah, 2025). Among these, snake venoms offer a highly diverse array of biochemical compounds that have evolved over millions of years through natural selection (Muttiah and Hanafiah, 2025; Abdullahi et al., 2023). Rather than using venom proteins directly as therapeutic agents, researchers are developing safer, more selective antimicrobial compounds based on these proteins as molecular templates (Ogujura et al., 2023). Recent advances in venomomics, peptide engineering, and synthetic biology have accelerated the discovery of venom-derived molecules with potent antibacterial and antibiofilm properties (Abdullahi et al., 2023; Cândido et al., 2026; Zhang, 2025).

Major Snake Venom-Derived Antimicrobial Molecules

Snake venoms contain diverse classes of proteins and peptides with notable antibacterial properties. Among these, phospholipases A₂ (PLA₂s) play a critical role by hydrolysing membrane phospholipids, thereby disrupting bacterial cell membranes. In addition to their enzymatic functions, certain peptides derived from PLA₂s exhibit membranolytic activity and have reduced toxicity compared with their native enzyme counterparts. This characteristic makes them promising candidates for the development of novel antimicrobial agents (de Melo Fernandes et al., 2024; Singkham-In et al., 2023).
L-amino acid oxidases (LAAOs) catalyse the oxidation of L-amino acids, generating hydrogen peroxide, which in turn induces oxidative stress that can damage bacterial membranes, proteins, and nucleic acids (de Melo Fernandes et al., 2024). LAAOs derived from Bothrops moojeni, Bothrops jararacussu, and Ophiophagus hannah have exhibited significant antibacterial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa, including inhibition of biofilm formation (de Melo Fernandes et al., 2024; da Silva Caldeira et al., 2021).
Among venom-derived antimicrobial molecules, snake cathelicidins are particularly notable for their promising antibacterial properties. These cationic amphipathic peptides interact rapidly with negatively charged bacterial membranes, leading to membrane destabilisation and leakage of intracellular contents (De Barros et al., 2019; Abdullahi et al., 2021). Cathelicidin-derived peptides from species such as Naja atra, Python bivittatus, Bungarus fasciatus, and Bothrops atrox exhibit broad-spectrum antibacterial activity against a range of pathogens, including Gram-positive and Gram-negative bacteria, as well as multidrug-resistant strains (De Barros et al., 2019; Cai et al., 2018; Van Hoek, 2014; Wang et al., 2023).
Recent research has shifted from evaluating native toxins to developing synthetic analogues, such as BotrAMP14 and CrotAMP14. These engineered peptides retain significant antibacterial efficacy while demonstrating reduced cytotoxicity and enhanced effectiveness against biofilm formation. This shift underscores the importance of rational peptide optimisation in the design of antimicrobial agents (Zhang, 2025; Cândido et al., 2026).

Activity Against Multidrug-Resistant Pathogens

Numerous venom-derived molecules have shown efficacy against clinically significant multidrug-resistant bacteria. L-amino acid oxidases (LAAOs) from Bothrops species have been reported to inhibit the growth of Staphylococcus aureus and disrupt established biofilms, while engineered cathelicidin-derived peptides exhibit potent antimicrobial activity against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and resistant Escherichia coli (da Silva Caldeira et al., 2021; de Melo Fernandes et al., 2024; Candido et al., 2026).
In contrast to traditional antibiotics, which typically target specific bacterial enzymes or metabolic pathways, many venom-derived peptides primarily disrupt bacterial membrane integrity (Abdullahi et al., 2021; 2023). This mechanism of action may reduce the likelihood of cross-resistance with existing antimicrobial classes and could enhance the effectiveness of conventional antibiotics when used in combination therapies (Bocian et al., 2020; Su et al., 2025). Nonetheless, bacterial adaptation through modifications in membrane composition and surface charge remains a valid concern, highlighting the need for ongoing surveillance and studies focused on resistance development (Su et al., 2025).

Veterinary Applications and One Health Perspective

The growing concern about antimicrobial resistance (AMR) in veterinary medicine has prompted renewed interest in alternative therapeutic strategies. One promising avenue is the use of venom-derived antimicrobial peptides (AMPs), which have shown potential for treating conditions including canine pyoderma, chronic wound infections, otitis externa, orthopaedic implant infections, bovine mastitis, and poultry bacterial diseases (Rabea et al., 2025; O’Connell et al., 2023). Notably, these peptides can disrupt bacterial biofilms, a feature that may prove invaluable for treating chronic infections where traditional antibiotics have limited efficacy (Brown et al., 2019; Roque-Borda et al., 2025).
From a One Health perspective, it is crucial to recognise that resistant bacteria circulate among companion animals, livestock, wildlife, humans, and the broader environment (Laxminarayan et al., 2013; Qasim et al., 2024). Therefore, the approach to developing novel antimicrobial agents must not only focus on creating new molecules but also integrate with existing frameworks for antimicrobial stewardship, surveillance, vaccination, infection prevention, and the responsible use of antimicrobials. This comprehensive strategy will ensure that new interventions complement rather than replace established control measures (WHO, 2023, 2024; Oliveira et al., 2024).

Current Challenges and Future Perspectives

Despite promising in vitro results, several challenges impede the clinical translation of venom-derived compounds. Native toxins frequently exhibit cytotoxicity and haemolytic activity, and they also face issues such as rapid degradation, poor pharmacokinetic properties, and high production costs (Ogujura et al., 2023; Falcao and Radis-Baptista, 2020). As a result, current research is focusing on strategies such as peptide engineering, amino acid substitution, peptide truncation, cyclisation, and the development of nanoparticle-based delivery systems to enhance both stability and therapeutic selectivity (Cândido et al., 2026; Magana et al., 2020; Zhang, 2025).
Additionally, the application of advanced computational techniques and high-throughput venomomics is expected to accelerate the discovery of novel antimicrobial candidates with improved safety profiles (Magana et al., 2020). Combining conventional antibiotics with other agents may further mitigate the development of antimicrobial resistance while enhancing antibacterial efficacy (Bocian et al., 2020; Magana et al., 2020).

Conclusions

Snake venoms are recognised as a remarkable natural reservoir of antimicrobial compounds, with promising applications in both veterinary and human medicine (Muttiah and Hanafiah, 2025; Ogujura et al., 2023). Recent developments suggest that engineered venom-derived peptides may be superior therapeutic candidates to their native counterparts, exhibiting potent antibacterial activity while minimising toxicity (Cândido et al., 2026; Zhang, 2025). Although no venom-derived antimicrobials have yet been adopted in routine veterinary clinical settings, advances in peptide engineering, nanotechnology, and drug delivery systems are paving the way for their future use as adjunctive strategies against antimicrobial resistance (Zhang, 2025; Magana et al., 2020). Within the framework of One Health, these bioactive molecules could play a significant role in integrated strategies targeting the global challenge of multidrug-resistant bacterial infections (Murray et al., 2022; Karnwall et al., 2025).

Author Contributions

Conceptualisation: B.B-M., P.M.; resources: B.B-M., P.M.; writing – original draft preparation: B.B-M., P.M.; writing – review and editing: B.B-M., P.M. The authors have read and agreed to the published version of the manuscript.

Funding

This study received no external funding.

Data Availability Statement

Data supporting the findings are available from the corresponding author on reasonable request.

Acknowledgments

The authors express their sincere gratitude to the Faculty of Veterinary Medicine, Stara Zagora, for the APC support.

Conflicts of Interest

The authors declare no conflicts of interest.

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