Mandel Shira, Michaeli Janna, Nur Noa, Erbetti Isabelle, Zazoun Jonathan, Ferrari Livia, Felici Antonio, Cohen-Kutner Moshe, Bachnoff Niv
Omnix Medical Ltd., High-Tech Village, Givat-Ram Campus, 9270401, Jerusalem, Israel.
Evotec Anti-Infective, Department of Microbiology Discovery, Aptuit (Verona) S.R.L., an Evotec Company, via A. Fleming 4, 37135, Verona, Italy.
Sci Rep. 2021 Mar 23;11(1):6603. doi: 10.1038/s41598-021-86155-9.
New antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.
迫切需要新型抗菌剂,尤其是用于消除代表大多数抗生素耐药性威胁的多重耐药革兰氏阴性菌。在以下研究中,我们展示了一种工程抗菌肽OMN6的卓越特性,它是一种基于天蚕素A的40个氨基酸的环肽,对革兰氏阴性菌具有高效杀菌作用机制。与基于小分子且结合特定酶或细菌位点的抗菌剂不同,OMN6的作用靶点被认为是细菌膜。此外,无论细菌基因型或耐药表型如何,OMN6的作用机制对鲍曼不动杆菌实验室菌株和临床分离株均有效,因此,从数量级来看,其由突变驱动的耐药性、复发或耐受性发展的可能性要小得多。OMN6在红细胞和HEK293T细胞上具有完全的安全裕度,稳定性增加且蛋白水解降解显著减少。综上所述,这些结果强烈表明OMN6是一种高效、稳定且无毒的新型抗菌剂,具有成为人类治疗药物的潜力。