Embryonic exposure to glycopeptides induces acute toxicity and developmental neurotoxicity in zebrafish (Danio rerio)

Glycopeptide antibiotics are crucial in combating severe bacterial infections. However, concerns persist regarding their environmental impact and potential toxicity to human health. This study explores the dosedependent toxicity of glycopeptide antibiotics on zebrafish embryos, revealing significant differences in developmental and neurological effects. Our findings indicate that oritavancin (ORI) and telavancin (TEL) exhibit greater acute toxicity compared to vancomycin (VAN). High doses of glycopeptides cause notable developmental abnormalities, including reduced body length and potential organ formation disruptions. TEL's prominent accumulation in embryos likely contributes to its heightened toxicity. The study also highlights differential effects on zebrafish locomotion, with ORI affecting sensory processing and motor control, TEL altering swimming time distribution, and VAN influencing inactivity and active swimming, varying by concentration and light-dark cycles. Molecular analyses, including RNA-seq and qRT-PCR, show that glycopeptides significantly alter gene expression related to nervous system development, particularly affecting sipa1l1, a gene essential for synaptic function and dendritic spine growth. The disruption of neurodevelopmental pathways suggests mechanisms through which these compounds influence development. These findings underscore the critical role of glycopeptide structure in toxicity and emphasize the need for further research to delineate specific affected molecular pathways, which could guide future studies and treatments for neurodevelopmental disorders.