Bacterial neurotoxins: The snake venoms of the microbial world-a clinical and bioengineering approach

The central and peripheral nervous systems constitute highly organized and dynamic networks that rely on precise regulation of synaptic transmission, membrane integrity, cytoskeletal stability, and intracellular signaling. Disruption of these tightly controlled processes can lead to a wide range of neurological disorders. Among the various modulators of neural function, bacterial neurotoxins represent a unique class of exotoxins that selectively target key neuronal components with remarkable molecular specificity. Traditionally studied in the context of infectious pathogenesis, bacterial neurotoxins are now increasingly recognized as powerful molecular probes of synaptic machinery and intracellular signaling pathways. In addition to their direct effects on neurons, accumulating evidence indicates that bacterial neurotoxins also participate in neuroimmune interactions, contribute to neuroinflammatory cascades, and may impact gut-brain axis signaling and long-term neurodegenerative vulnerability. Advances in structural biology and protein engineering have shifted the field from descriptive toxicology to translational neurobiology. Engineered toxin derivatives and attenuated catalytic variants are being investigated as tools for neural circuit modulation, targeted drug delivery, and the treatment of movement disorders, chronic pain, and other neurological conditions. This review offers a comprehensive and critical synthesis of bacterial neurotoxins, integrating molecular mechanisms of action with their pathological consequences, emerging research and therapeutic applications. By combining insights from infectious disease biology and systems neuroscience, we seek to outline both the opportunities and the unresolved challenges that shape the future direction of bacterial neurotoxin research in precision neurology.