2026-04-05T10:47:50Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/2274082026-03-01T23:12:12Zcom_2072_1057col_2072_478917col_2072_478933
B-rich colistin and B-pure colistin as novel strategies to increase thetherapeutic window of polymyxin antibiotic therapy
Guzman, Laura
Rabanal Anglada, Francesc
Garcia, Júlia
Marqués Villavecchia, Ana M.
Sánchez-López, E. (Elena)
Cano Fernández, Amanda
Cajal Visa, Yolanda
Camins Espuny, Antoni
Ettcheto Arriola, Miren
Barenys Espadaler, Marta
Neurotoxicologia
Antibiòtics
Antioxidants
Neurotoxicology
Antibiotics
Antioxidants
The rise of multidrug-resistant bacteria has made necessary the reintroduction of legacy antibiotics, such as</p><p>colistin, only used as last-resort due to its concerning derived nephro- and neuro-toxicities. This lipopeptide</p><p>antibiotic is primarily composed of two main components, colistin A and colistin B. However, their individual</p><p>toxicological profiles remain poorly understood. This study explores the potential of purified colistin B as a safer</p><p>alternative to the current colistin-based antibiotic therapy. Using the zebrafish embryo model, we assessed and</p><p>compared the lethality and neurotoxic effects of two colistin mixtures formulations with different proportions of</p><p>colistin A and B, and the toxicities of both purified primary components. Additionally, we investigated their</p><p>respective mechanisms of toxicity and the possibility of preventing their toxic effects using three antioxidant</p><p>compounds. In zebrafish embryos, colistin B has a significantly lower toxicity profile than colistin A, and in</p><p>accordance, a colistin mixture mainly composed of colistin B induces significantly less toxicity than a mixture</p><p>with colistin A as the main component. Moreover, the A-rich colistin mixture significantly increased AChE activity</p><p>whereas the B-rich colistin mixture did not. Furthermore, we demonstrate for the first time that colistin A</p><p>and colistin B have distinct mechanisms of toxicity. Notably, only colistin B toxicity is preventable by preexposure</p><p>to antioxidant compounds, whereas co-exposure provides no protective effect. Our findings open a</p><p>new door towards B-rich or B-pure colistin-based formulations as safer alternatives to current polymyxin therapies,</p><p>potentially improving their therapeutic window by reducing their adverse effects.
2026-02-25T12:41:56Z
2026-02-25T12:41:56Z
2025-07-15
2026-02-25T12:41:57Z
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Versió postprint del document publicat a: https://doi.org/10.1016/j.biopha.2025.118366
Biomedicine & Pharmacotherapy, 2025, vol. 190, p. 118366
https://doi.org/10.1016/j.biopha.2025.118366
cc by (c) Guzman, Laura, et al, 2025
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Elsevier Masson SAS