Cebrián Rubén, Martínez-García Marta, Fernández Matilde, García Federico, Martínez-Bueno Manuel, Valdivia Eva, Kuipers Oscar P, Montalbán-López Manuel, Maqueda Mercedes
Department of Clinical Microbiology, Instituto de Investigación Biosanitaria Ibs.GRANADA, University Hospital San Cecilio, Granada, Spain.
Department of Molecular Genetics, University of Groningen, Groningen, Netherlands.
Front Microbiol. 2023 Feb 2;14:1110360. doi: 10.3389/fmicb.2023.1110360. eCollection 2023.
Antimicrobial resistance is a natural and inevitable phenomenon that constitutes a severe threat to global public health and economy. Innovative products, active against new targets and with no cross- or co-resistance with existing antibiotic classes, novel mechanisms of action, or multiple therapeutic targets are urgently required. For these reasons, antimicrobial peptides such as bacteriocins constitute a promising class of new antimicrobial drugs under investigation for clinical development. Here, we review the potential therapeutic use of AS-48, a head-to-tail cyclized cationic bacteriocin produced by . In the last few years, its potential against a wide range of human pathogens, including relevant bacterial pathogens and trypanosomatids, has been reported using tests and the mechanism of action has been investigated. AS-48 can create pores in the membrane of bacterial cells without the mediation of any specific receptor. However, this mechanism of action is different when susceptible parasites are studied and involves intracellular targets. Due to these novel mechanisms of action, AS-48 remains active against the antibiotic resistant strains tested. Remarkably, the effect of AS-48 against eukaryotic cell lines and in several animal models show little effect at the doses needed to inhibit susceptible species. The characteristics of this molecule such as low toxicity, microbicide activity, blood stability and activity, high stability at a wide range of temperatures or pH, resistance to proteases, and the receptor-independent effect make AS-48 unique to fight a broad range of microbial infections, including bacteria and some important parasites.
抗菌耐药性是一种自然且不可避免的现象，对全球公共卫生和经济构成严重威胁。迫切需要创新产品，这些产品针对新靶点起作用，与现有抗生素类别无交叉耐药或共同耐药，具有新的作用机制或多个治疗靶点。基于这些原因，诸如细菌素之类的抗菌肽构成了一类有前景的新型抗菌药物，正在进行临床开发研究。在此，我们综述了AS - 48的潜在治疗用途，AS - 48是由……产生的一种头尾环化的阳离子细菌素。在过去几年中，已经通过……试验报道了其对多种人类病原体的潜在作用，包括相关细菌病原体和锥虫，并且对其作用机制进行了研究。AS - 48可在不借助任何特异性受体介导的情况下在细菌细胞膜上形成孔道。然而，在研究易感寄生虫时，这种作用机制有所不同，涉及细胞内靶点。由于这些新的作用机制，AS - 48对所测试的抗生素耐药菌株仍保持活性。值得注意的是，在抑制易感物种所需的剂量下，AS - 48对真核细胞系和几种动物模型的影响很小。该分子具有低毒性、杀微生物活性、血液稳定性和活性、在广泛温度或pH范围内的高稳定性、对蛋白酶的抗性以及不依赖受体的作用等特性，使得AS - 48在对抗包括细菌和一些重要寄生虫在内的广泛微生物感染方面独具特色。
