Cebrián Rubén, Rodríguez-Cabezas M Elena, Martín-Escolano Rubén, Rubiño Susana, Garrido-Barros María, Montalbán-López Manuel, Rosales María José, Sánchez-Moreno Manuel, Valdivia Eva, Martínez-Bueno Manuel, Marín Clotilde, Gálvez Julio, Maqueda Mercedes
Department of Molecular Genetics, Faculty of Science and Engineering, Nijenborgh 7, 9747 AG, University of Groningen, Groningen, the Netherlands.
CIBER-EHD, Department of Pharmacology. Centre for Biomedical Research (CIBM), Avda del Conocimiento s/n, University of Granada, Granada, Spain.
J Adv Res. 2019 Jul 4;20:129-139. doi: 10.1016/j.jare.2019.06.003. eCollection 2019 Nov.
The antimicrobial potency of the bacteriocin AS-48 is well documented, but its clinical application requires investigation, as its toxicity could be different in (haemolytic and antibacterial activity in blood and cytotoxicity towards normal human cell lines) and (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 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.
细菌素AS-48的抗菌效力已有充分文献记载，但其临床应用仍需研究，因为其毒性在（血液中的溶血和抗菌活性以及对正常人细胞系的细胞毒性）和（如小鼠和斑马鱼胚胎）模型中可能有所不同。总体而言，所获得的结果很有前景。它们显示，在治疗浓度（高达27μM）下，AS-48导致细胞死亡或阻碍细胞生长的倾向可忽略不计，并且由于其在低浓度（0.3 - 8.9μM范围内）的选择性和效力，支持了这种肽作为抗多种微生物感染潜在治疗剂的适用性。此外，AS-48在全血中表现出低溶血活性，并且在未刺激的RAW巨噬细胞中不诱导亚硝酸盐积累，表明缺乏促炎作用。斑马鱼胚胎对AS-48意外的高敏感性可能是由于这些细胞的低分化状态。AS-48的低细胞毒性、小鼠皮肤致敏后淋巴细胞增殖的缺乏以及在小鼠模型中的无毒性，支持将广谱抗菌肽AS-48视为控制大量微生物感染，特别是那些涉及皮肤和软组织疾病的有前景的治疗剂。
