RT Journal Article
T1 Preclinical studies of toxicity and safety of the AS-48 bacteriocin.
A1 Cebrián, Rubén
A1 Rodríguez-Cabezas, M Elena
A1 Martín-Escolano, Rubén
A1 Rubiño, Susana
A1 Garrido-Barros, María
A1 Montalbán-López, Manuel
A1 Rosales, María José
A1 Sánchez-Moreno, Manuel
A1 Valdivia, Eva
A1 Martínez-Bueno, Manuel
A1 Marín, Clotilde
A1 Gálvez, Julio
A1 Maqueda, Mercedes
K1 Antimicrobial peptides
K1 Cytotoxicity
K1 Haemolysis
K1 Mouse model
K1 Topical delivery
K1 Zebrafish model
AB 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 (up to 27 μM) 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 the range of 0.3-8.9 μM). 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 AS-48 as a promising therapeutic agent for the control of a vast array of microbial infections, in particular, those involved in skin and soft tissue diseases.
SN 2090-1232
YR 2019
FD 2019-07-04
LK http://hdl.handle.net/10668/14338
UL http://hdl.handle.net/10668/14338
LA en
DS RISalud
RD Apr 6, 2025