Preclinical studies of toxicity and safety of the AS-48 bacteriocin
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AuthorCebrián, Rubén; Rodríguez-Cabezas, M. Elena; Martín-Escolano, Rubén; Rubiño, Susana; Garrido Barros, María; Montalbán-López, Manuel; Rosales Lombardo, María José; Sánchez Moreno, Manuel; Valdivia, Eva; Martínez Bueno, Manuel; Marín Sánchez, Clotilde; Gálvez Peralta, Julio Juan; Maqueda Abreu, Mercedes
CytotoxicityAntimicrobial peptidesTopical deliveryZebrafish modelMouse model
Cebrián, R., Rodríguez-Cabezas, M. E., Martín-Escolano, R., Rubiño, S., Garrido-Barros, M., Montalbán-López, M., ... & Marín, C. (2019). Preclinical studies of toxicity and safety of the AS-48 bacteriocin. Journal of advanced research, 20, 129-139.
SponsorshipThis research was funded by the Spanish Ministry of Economy and Competitiveness (SAF2013-48971-C2-1-R, CSD2010-00065, and AGL2015-67995-C3-3-R, all including funds from the European Regional Development Funding, ERDF) and by the Research Groups (BIO160, CTS 944 and CTS 164, UGR) from Junta de Andalucía (Spain). The CIBER-EHD is funded by the Instituto de Salud Carlos III. RM-E is grateful for an FPU Grant (FPU14/01537) from the Ministry of Education, (Spain).
The in vitro antimicrobial potency of the bacteriocin AS-48 is well documented, but its clinical application requires investigation, as its toxicity could be different in in vitro (haemolytic and antibacterial activity in blood and cytotoxicity towards normal human cell lines) and in vivo (e.g. mice and zebrafish embryos) models. Overall, the results obtained are promising. They reveal the negligible propensity of AS-48 to cause cell death or impede cell growth at therapeutic concentrations and support the suitability of this peptide as a potential therapeutic agent against several microbial infections, due to its selectivity and potency at low concentrations. In addition, AS-48 exhibits low haemolytic activity in whole blood and does not induce nitrite accumulation in non-stimulated RAW macrophages, indicating a lack of pro-inflammatory effects. The unexpected heightened sensitivity of zebrafish embryos to AS-48 could be due to the low differentiation state of these cells. The low cytotoxicity of AS-48, the absence of lymphocyte proliferation in vivo after skin sensitization in mice, and the lack of toxicity in a murine model support the consideration of the broad spectrum antimicrobial peptide