Friends or Foes? Emerging Impacts of Biological Toxins

Abstract

Toxins are substances produced from biological sources (e.g., animal, plants, microorganisms) that have deleterious effects on a living organism. Despite the obvious health concerns of being exposed to toxins, they are having substantial positive impacts in a number of industrial sectors. Several toxin-derived products are approved for clinical, veterinary, or agrochemical uses. This review sets out the case for toxins as 'friends' that are providing the basis of novel medicines, insecticides, and even nucleic acid sequencing technologies. We also discuss emerging toxins ('foes') that are becoming increasingly prevalent in a range of contexts through climate change and the globalisation of food supply chains and that ultimately pose a risk to health. Toxins and Toxinology In the natural world, toxins are employed for diverse purposes, from the prey-incapacitating molecules found in snake, spider, and cone snail venom, to the defensive compounds harboured by numerous poisonous plant and animal species. While the consequences of human intoxication can be severe (Box 1), the functional diversity of biological toxins has led to their frequent use as experimental tools for studying physiological and pharmacological mechanisms (e.g., synaptic transmission, ion channel subtypes) (Figure 1). Toxinology involves the identification, characterisation, production, and engineering of biological toxins along with their application or repurposing as research tools and clinical products. As such, toxinology encompasses the study of the evolution, chemistry, biology, and clinical effects of toxins and includes potential biotechnological and/or therapeutic applications. Experimental applications of toxins as tools for physiologists go back a long time, including Claude Bernard's experiments in the 1800s with curare to demonstrate the existence of chemical signalling between nerves and muscles [2], and Henry Dale's use of muscarine and nicotine to show different subtypes of receptors for acetylcholine [3]. Snake toxins were critical for the first isolation of a receptor for a neurotransmitter [a-bungarotoxin and nicotinic acetylcholine receptors (nAChRs)] [4]. Recently, peptide toxins have been very useful in teasing out the functional importance of different subtypes of ion channels that are critical for neuronal function and cellular signalling [5-7]. An increasing number of toxins are now transitioning from the laboratory to the clinic and the balance of research in this aspect of toxinology is shifting from the classical development of anti-toxins and anti-venoms towards drug discovery [8,9]. The attraction of toxins for drug discovery lies in their often unique selectivity of their biological effects coupled with high potency. Toxic plant alkaloids were the first source of toxin-derived therapeutics, notably

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

“…In solenodons, venom also appears to facilitate prey capture, but additional work is required to fully elucidate the nature of this venom, such as 1) compiling extensive natural history observations of foraging behavior; 2) testing solenodon venom on natural prey items; 3) comparisons of venom composition and function between the 2 solenodon species, and between male and female individuals; and 4) further investigation of solenodon dental and mandibular morphology to understand their prey handling capability. Nonetheless, our findings highlight the evolutionary novelty of the solenodon venom system and stress the importance of studying and conserving endangered species in order to protect both ecological diversity and their utilitarian value, which in this case is most relevant when considering the bioactive compounds found in their toxic secretions (7, 55). Ultimately, our work reveals a surprising case of convergent molecular evolution, whereby KLK1 s have been independently recruited for use in the nonhomologous venom systems of shrews and solenodons.…”

“…Venoms have proven to be valuable systems for understanding a variety of different evolutionary processes, including those relating to convergence (1, 2), accelerated molecular evolution (3), gene duplication (4), and protein neofunctionalization (5). Venoms are also of great medical importance, both due to the harm they can cause to people (e.g., >100,000 people die annually as a result of snake envenoming) (6) and for the value of their highly selective toxins for understanding physiological processes and the development of new pharmaceuticals (7).…”

From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery

“…The cosmeceutical field is a profitable venture. For example, the anti-wrinkling effect of the botulinum toxin (Botox ® ), a toxin isolated from Clostridium botulinum bacteria, accounts for striking global sales of about $3 billion per year (Clark et al, 2019). Among the biologically active compounds from animal venoms showing cosmeceuticals applications, we can cite the use of bee venom-containing cosmetics on facial wrinkles in human skin (Han et al, 2015), and the inhibitory activity of melanogenesis of Argiotoxine-636 (ArgTX-636), a polyamine isolated from Argiope lobata spider venom (Verdoni et al, 2016), including a deposited patent (US10064814B2) for skin whitening/ depigmenting (Mabrouk et al, 2018).…”

Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

“…The purification of bioactive compounds rendered small yields, such that only the more abundant compounds were detected and used in research, even if low-abundance molecules had a critical role in toxicity. Many of these new ‘omic’ approaches have reduced the amount of starting material needed for the analysis, making it affordable for venom studies [129,130,131,132]. In depth analysis of venoms from long-neglected organisms using these techniques not only increases the knowledge about venom composition, phylogeny, and evolution, but also allows the identification of underrepresented toxins which may exert unique biological properties and hold potential applications.…”