ToxinsPub Date : 2025-05-07DOI: 10.3390/toxins17050232
Min An, Xin Cheng, Yu Zhang, Jiang Gu, Xuhu Mao
{"title":"BLF1 Affects ATP Hydrolysis Catalyzed by Native and Mutated eIF4A1 and eIF4A2 Proteins.","authors":"Min An, Xin Cheng, Yu Zhang, Jiang Gu, Xuhu Mao","doi":"10.3390/toxins17050232","DOIUrl":"10.3390/toxins17050232","url":null,"abstract":"<p><p><i>Burkholderia</i> lethal factor 1 (BLF1), a toxin derived from <i>Burkholderia pseudomallei</i>, reacts with eukaryotic initiation factor (eIF) 4A to inhibit protein synthesis. eIF4A1 and eIF4A2 are involved in translation initiation and share over 90% sequence similarity. However, they exert distinct effects on cancer treatment outcomes. To understand the molecular mechanism by which BLF1 modulates eIF4A isoforms in cancer cells, we investigated its effects on eIF4A-mediated adenosine 5'-triphosphate (ATP) hydrolysis. We found that eIF4A1 has a higher ATP-binding affinity compared to eIF4A2 (K<sub>m</sub> = 6.55 ± 0.78 μM vs. K<sub>m</sub> = 11.61 ± 2.33 μM). Meanwhile, we also found that eIF4A1 is more sensitive to changes in temperature, pH, and Mg<sup>2+</sup> concentration. Through N-terminal swapping and single amino acid mutations, we found that leucine 98 (L98) and alanine 100 (A100) play important roles in the ATPase activities of eIF4A isoforms. Moreover, BLF1 treatment significantly enhanced eIF4A2-mediated ATP hydrolysis at all tested ATP concentrations. These differences in BLF1-regulated eIF4A isoforms may explain its selective cytotoxicity against cancer cells. Our findings provide molecular insights into the functional difference between eIF4A isoforms and suggest that BLF1 might be of promising value for anticancer therapies.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-06DOI: 10.3390/toxins17050230
Gregory S Nicholson, David Canty, Annemarie Southern, Kevin Whelan, Amy D Brideau-Andersen, Ron S Broide
{"title":"Preclinical Evaluation of Botulinum Toxin Type E (TrenibotulinumtoxinE) Using the Mouse Digit Abduction Score (DAS) Assay.","authors":"Gregory S Nicholson, David Canty, Annemarie Southern, Kevin Whelan, Amy D Brideau-Andersen, Ron S Broide","doi":"10.3390/toxins17050230","DOIUrl":"10.3390/toxins17050230","url":null,"abstract":"<p><p>TrenibotulinumtoxinE (trenibotE), a botulinum neurotoxin serotype E (BoNT/E), is being developed for clinical use, and can fill a unique treatment gap for patients who are seeking neurotoxin treatment with a rapid onset and short duration of effect. This preclinical study characterized the pharmacological activity of trenibotE using the mouse Digit Abduction Score (DAS) assay. A comparative analysis was also performed between trenibotE and an equi-efficacious dose of the botulinum neurotoxin serotype A (BoNT/A) onabotulinumtoxinA (onabotA). TrenibotE showed a dose-dependent increase in peak DAS and duration of effect. A comparison of onabotA and trenibotE in this assay at approximate equi-efficacious doses showed trenibotE to have a faster onset of effect (trenibotE yielded a significantly greater effect as early as 6 h post-injection), shorter time to peak effect (24-27 h vs. 2 days), and an overall shorter duration of response (3 days vs. 14 days). The unique temporal characteristics of trenibotE and pharmacological differentiation from onabotA observed in this preclinical assay support the clinical development of this molecule.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxin Accumulation, Distribution, and Sources of Toxic Xanthid Crabs.","authors":"Yuchengmin Zhang, Hongchen Zhu, Tomohiro Takatani, Osamu Arakawa","doi":"10.3390/toxins17050228","DOIUrl":"10.3390/toxins17050228","url":null,"abstract":"<p><p>Several species of crabs from the Xanthidae family are recognized as dangerous marine organisms due to their potent neurotoxins, including paralytic shellfish toxin (PST), tetrodotoxin (TTX), and palytoxin (PLTX). However, the mechanisms of toxin accumulation and transport and the origin of these toxins in toxic xanthid crabs remain unknown. The identification of toxic crab species, their toxicity and toxin composition, and toxin profiles have been studied thus far. To date, more than ten species of xanthid crabs have been confirmed to possess toxins. Recently, several new studies on crabs, including the geographic distribution of toxin profiles and the ecological role of crabs, have been reported. Therefore, this review provides a summary of global research on toxic xanthid crabs, containing new findings and hypotheses on the toxification in and the origins of these crabs. Furthermore, the challenges and future perspectives in this field are also discussed.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-05DOI: 10.3390/toxins17050229
Ye-Seul Lee, Yoon Jae Lee, In-Hyuk Ha
{"title":"Therapeutic Potential of <i>Scolopendra subspinipes</i>: A Comprehensive Scoping Review of Its Bioactive Compounds, Preclinical Pharmacology, and Clinical Applications.","authors":"Ye-Seul Lee, Yoon Jae Lee, In-Hyuk Ha","doi":"10.3390/toxins17050229","DOIUrl":"10.3390/toxins17050229","url":null,"abstract":"<p><p><i>Scolopendra subspinipes</i>, commonly known as the Chinese red-headed centipede, has been utilized in traditional East Asian medicine for centuries to treat conditions such as chronic pain, inflammation, convulsions, and infections. Recent pharmacological investigations have uncovered a wide array of bioactive molecules-including peptides, alkaloids, and polysaccharide-protein complexes-from both venom and whole-body extracts. This review synthesizes findings from 45 in vitro, in vivo, and clinical studies investigating the pharmacological effects of venom-derived and whole-body-derived compounds from <i>S. subspinipes</i> across multiple domains, including analgesic, anti-inflammatory, antimicrobial, antifungal, antioxidant, antitumor, antithrombotic, anti-fibrotic, and neuroprotective activities, along with a brief scoping review of clinical practice guidelines. Key venom-derived compounds such as the peptide SsmTX-I, immunomodulatory antimicrobial peptide scolopendrasin IX, and antitumor peptide scolopentide exhibit strong mechanistic rationale and preclinical efficacy, positioning them as lead candidates for clinical development. Compounds derived from whole-body extracts, including alkaloids and polysaccharide-protein complexes, also demonstrate promising therapeutic potential. Mechanistic studies suggest these compounds operate via distinct pathways-such as ion-channel inhibition, NF-κB suppression, and apoptosis induction-offering potential advantages over existing therapies. However, current evidence remains primarily preclinical, and challenges such as extract variability, immunogenicity, and lack of standardized dosing must be addressed. Future research should prioritize isolation and structural optimization of key peptides, standardized formulation development, toxicological profiling, and early-phase human trials. The integration of traditional knowledge and modern pharmacological insights underscores the potential of venom- and whole-body-derived <i>S. subspinipes</i> agents to enrich the drug discovery, particularly for conditions with unmet therapeutic needs.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-04DOI: 10.3390/toxins17050227
Felipe Penagos-Tabares, Anastasija Todorov, Jog Raj, Hunor Farkaš, Goran Grubješić, Zdenka Jakovčević, Svetlana Ćujić, Jelena Nedeljković-Trailović, Marko Vasiljević
{"title":"Multi-Mycotoxin Contamination in Serbian Maize During 2021-2023: Climatic Influences and Implications for Food and Feed Safety.","authors":"Felipe Penagos-Tabares, Anastasija Todorov, Jog Raj, Hunor Farkaš, Goran Grubješić, Zdenka Jakovčević, Svetlana Ćujić, Jelena Nedeljković-Trailović, Marko Vasiljević","doi":"10.3390/toxins17050227","DOIUrl":"10.3390/toxins17050227","url":null,"abstract":"<p><p>Mycotoxin contamination in maize poses significant food and feed safety risks, particularly in regions with variable climatic conditions like Serbia. This study investigated the occurrence of regulated mycotoxins in maize harvested across the Republic of Serbia from 2021 to 2023, emphasizing the impact of climatic factors. A total of 548 samples of unprocessed maize grains were analysed for the presence of key mycotoxins, including aflatoxins, ochratoxin A, zearalenone, deoxynivalenol, fumonisins, and trichothecenes type A (T-2 and HT-2 toxins), using validated analytical methods. The results revealed high contamination frequencies, with aflatoxins and fumonisins being the most prevalent. The results revealed substantial temporal variability and frequent co-contamination of mycotoxins. Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) was the most concerning contaminant, with 73.2% of the samples in 2022 exceeding the European regulatory limit for human consumption (5 µg/kg) for un processed maize grains, reaching peak concentrations of 527 µg/kg, which is 105.4 times higher than the allowed limit. For animal feed, the limit of 20 µg/kg was exceeded in 40.5% of the samples, with the highest concentration being 26.4 times greater than the maximum allowable level. In 2021, the non-compliance rates for AFB<sub>1</sub> in food and feed were 8.3% and 2.3%, respectively, while in 2023, they were 23.2% and 12.2%, respectively. Fumonisins contamination was also high, particularly in 2021, with fumonisin B<sub>1</sub> (FB<sub>1</sub>) detected in 87.1% of samples and average concentrations reaching 4532 µg/kg. Although levels decreased in 2023 (70.7% occurrence, average 885 µg/kg), contamination remained significant. Deoxynivalenol (DON) contamination was consistently high (>70% of samples), with peak concentrations of 606 µg/kg recorded in 2021. Zearalenone (ZEN) and ochratoxin A (OTA) occurred less frequently, but ZEN levels peaked in 2022 at 357.6 µg/kg, which is above the regulatory limit of 350 µg/kg for food. Trichothecenes (HT-2 and T-2 toxins) were detected sporadically, with concentrations well below critical thresholds. Co-occurrence of mycotoxins was frequent, with significant mixtures detected, particularly between aflatoxins and fumonisins, as well as other fusarial toxins. The analysis demonstrated that temperature, humidity, and rainfall during both the growing and harvest seasons strongly influenced mycotoxin levels, with the most severe contamination occurring under specific climatic conditions. Notably, the highest mycotoxin levels, like aflatoxins, were linked to warmer temperatures and lower rainfall. The high non-compliance rates for aflatoxins and fumonisins and co-contamination pose significant food and feed safety risks. From a public health perspective, chronic exposure to contaminated maize increases the likelihood of carcinogenesis and reproductive disorders. Reduced productivity and bioaccumulation in animal tissues/products repr","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-03DOI: 10.3390/toxins17050225
Calogero Malfitano, Antonio Robecchi Majnardi, Arianna Pesaresi, Vincenzo Ricci
{"title":"Ultrasound-Guided Botulinum Toxin Injections for Hand Spasticity: A Technical Guide for the Dorsal Approach.","authors":"Calogero Malfitano, Antonio Robecchi Majnardi, Arianna Pesaresi, Vincenzo Ricci","doi":"10.3390/toxins17050225","DOIUrl":"10.3390/toxins17050225","url":null,"abstract":"<p><p>Spasticity often occurs following neurological disorders such as traumatic brain injury, cerebral palsy, and stroke. Botulinum toxin (BTX) injections, especially when paired with rehabilitation, are among the most effective interventions for these patients. Various techniques for administering BTX injections to the upper limb muscles have been described. However, a standardized method for ultrasound-guided injections in the intrinsic muscles of the hand remains quite scant in the literature. The authors suggest a novel dorsal approach to treat the most common abnormal postural patterns in hand spasticity, thumb-in-palm, and intrinsic plus. This approach facilitates access to the muscles while minimizing patient discomfort, as it avoids the need to open forcibly the spastic hand. The adductor pollicis, flexor pollicis brevis, lumbrical, and interosseus muscles have been identified as primary anatomical targets to improve hand posture and function. Standardized sonographic scans are leveled with anatomical illustrations and probe/patient positioning images for interventional procedures. Additionally, tips and techniques for promptly identifying vascular bundles are included to enhance the safety of the procedures. This technical report aims to provide an easy and ready-to-use tool in clinical practice for injecting intrinsic hand muscles in spastic patients, utilizing a novel dorsal approach.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-03DOI: 10.3390/toxins17050226
María Viñas, Petr Karlovsky
{"title":"A Comprehensive Review of Hypotheses About the Biological Function of Zearalenone, and a New Hypothesis for the Function of Resorcylic and Dihydroxyphenylacetic Macrolactones in Fungi.","authors":"María Viñas, Petr Karlovsky","doi":"10.3390/toxins17050226","DOIUrl":"10.3390/toxins17050226","url":null,"abstract":"<p><p>The special metabolite of <i>Fusarium</i> spp. zearalenone (ZEN) exerts estrogenic effects on mammals, stimulates plant growth, stimulates sexual development in fungi, and inhibits fungal growth. These activities inspired hypotheses about the biological function of ZEN. We briefly review the discovery of ZEN and its implications. The main subject of this review is a critical assessment of the hypotheses that ZEN is a fungal hormone, a plant hormone, a virulence factor, or a fungal defense metabolite. Conceptual and technical issues related to testing these hypotheses, such as inadequate analytical methods, confusion of incidental effects with biological functions, and lack of normalization, are illuminated. Based on these considerations, gene knockout experiments, and on the effects of biotic interactions on ZEN synthesis, we argue that ZEN is a defense metabolite protecting <i>Fusarium</i> spp. against mycoparasites and competitors. Similar reasoning and published data suggest that the <i>Fusarium</i> metabolite fusaristatin A fulfils the same function. Fungi produce many macrolactones of resorcylic acid (RALs) and dihydroxyphenylacetic acid (DHPLs) with properties similar to ZEN. Their widespread occurrence, antifungal activity, and further considerations prompt us to hypothesize that the fundamental function of fungal RALs and DHPLs lies in defense and interference competition.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-02DOI: 10.3390/toxins17050224
Lee Jones, Bryan G Fry
{"title":"Consistent Killers: Conservation of Thrombin-Like Action on Fibrinogen by Bushmaster (<i>Lachesis</i> Species) Venoms Underpins Broad Antivenom Cross-Reactivities.","authors":"Lee Jones, Bryan G Fry","doi":"10.3390/toxins17050224","DOIUrl":"10.3390/toxins17050224","url":null,"abstract":"<p><p>Snakebite represents a significant public health challenge in Central and South America, with <i>Lachesis</i> (Bushmaster) species posing unique clinical challenges due to their severe envenomation effects arising from a combination of potent venom and copious venom yields. Using in vitro coagulation assays, we analyzed the coagulotoxic venom effects from four distinct localities: <i>L. muta</i> from Surinam and French Guiana and <i>L. stenophrys</i> from Costa Rica and Panama. This study examined the venom's impact on human plasma and fibrinogen and evaluated the efficacy of two regionally available antivenoms (PoliVal-ICP and Antivipmyn-Tri) in neutralizing the pathophysiological effects. Our results demonstrated a remarkable consistency in the pseudo-procoagulant venom activity (also known as: thrombin-like) across different species and localities. Antivenom efficacy testing revealed that both the PoliVal-ICP and Antivipmyn-Tri antivenoms effectively neutralized the venom effects across localities for both species, with the ICP antivenom showing the highest neutralization capacity. These toxicology findings highlight the biochemical conservation of venom composition across <i>Lachesis</i> species which underpins effective cross-neutralization in antivenom treatment.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-02DOI: 10.3390/toxins17050223
Suhe Dong, Danli Liu, Runfeng Lin, Yingjie Zhu, Peihong Zhu, Xin Jiang, Jie Mao, Yanqing Cao, Jing Peng, Tianyue Zhao, Danning Shen, Tao Li, Kun He, Na Wang
{"title":"Bongkrekic Acid and Its Novel Isomers: Separation, Identification, and Determination in Food Matrices.","authors":"Suhe Dong, Danli Liu, Runfeng Lin, Yingjie Zhu, Peihong Zhu, Xin Jiang, Jie Mao, Yanqing Cao, Jing Peng, Tianyue Zhao, Danning Shen, Tao Li, Kun He, Na Wang","doi":"10.3390/toxins17050223","DOIUrl":"10.3390/toxins17050223","url":null,"abstract":"<p><p>The toxicity associated with bongkrekic acid (BKA) is severe due to its chemical structure, which also facilitates high mortality rates; however, its isomer, isobongkrekic acid (iBKA), with only minor structural variance, demonstrates marked differences in toxicity. This discrepancy in structural properties and toxicity highlights that risks have been potentially underestimated within current detection standards for BKAs. In this study, a novel BKA trans isomer at the C8 and C9 double carbon bonds (E-configuration), termed iBKA-neo, was successfully separated and identified. Subsequently, the multiple reaction monitoring parameters and chromatographic conditions for three BKA isomers were optimized, enabling effective separation within 15 min via UHPLC-MS/MS, among which the ammonium positive adduct ions yielded significantly higher response intensities for all BKA isomers than traditional deprotonated molecules. Additionally, distinct differences in the ion ratios between iBKA-neo and BKA were utilized for preliminary screening. On this basis, the extraction and enrichment strategies for BKAs were optimized in food matrices and validated comprehensively with good linearity (0.25-500 μg/kg), a superior limit of quantification (0.25 μg/kg), acceptable recoveries (82.32-114.84%), and stable intraday and interday precision (an RSD less than 12.67%). These findings significantly contribute to ecotoxicology and the formulation of safety standards concerning BKAs.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12115625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ToxinsPub Date : 2025-05-01DOI: 10.3390/toxins17050221
Barathan Muttiah, Alfizah Hanafiah
{"title":"Snake Venom Compounds: A New Frontier in the Battle Against Antibiotic-Resistant Infections.","authors":"Barathan Muttiah, Alfizah Hanafiah","doi":"10.3390/toxins17050221","DOIUrl":"10.3390/toxins17050221","url":null,"abstract":"<p><p>The occurrence of antibiotic-resistant bacteria is a serious global health issue, and it emphasizes the need for novel antimicrobial agents. This review explores the potential of snake venom as another alternative strategy against antimicrobial resistance. Snake venoms are complex combinations of bioactive peptides and proteins, including metalloproteases (MPs), serine proteases (SPs), phospholipase A<sub>2</sub> (PLA<sub>2</sub>) enzymes, three-finger toxins (3FTXs), cysteine-rich secretory proteins (CRISPs), L-amino acid oxidases (LAAOs), and antimicrobial peptides (AMPs). The antibacterial products possess wide-spectrum antibacterial activity against resistant microbes via diverse mechanisms such as cell membrane disruption, enzymatic hydrolysis of microbial structures, generation of oxidative stress, inhibition of biofilms, and immunomodulation. Strong antimicrobial activity is reported by most studies, but these are mostly restricted to in vitro testing with low translational use. Although preliminary insights into molecular targets and physiological effects exist, further studies are needed to clarify long-term safety and therapeutic potential. Special attention is given to snake venom-derived extracellular vesicles (SVEVs), which enhance the therapeutic potential of venom toxins by protecting them from degradation, improving bioavailability, and facilitating targeted delivery. Furthermore, innovative delivery strategies such as PEGylation, liposomes, hydrogels, microneedle patches, biopolymer films, and nanoparticles are discussed for their role in reducing systemic toxicity and enhancing antimicrobial efficacy. The rational modification of venom-derived peptides further expands their therapeutic utility by improving pharmacokinetics and minimizing off-target effects. Together, these approaches highlight the translational potential of snake venom-based therapies as next-generation antimicrobials in the fight against resistant infections. By outlining these challenges and directions, this review positions snake venom as an overlooked but fertile resource in the battle against antibiotic resistance.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"17 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}