多重耐药细菌的兴起对世界人口造成了严重威胁。最近的报道已经确定了显示出对抗生素的泛耐药性的细菌菌株,并在医疗健康专家中引起了人们的担忧,即人类正处于进入后抗生素时代的黎明。目前,全球研究的重点是延长现有抗生素的寿命,以及开发新的抗微生物剂,以解决抗微生物耐药性问题。在本研究中,我们设计了一种新的共有肽,命名为“Pepcon”,通过在一个高度同源的蝎子抗菌肽组的成员之间的肽共有序列测定。发现该组的成员具有中等的抗微生物活性,对哺乳动物细胞具有显着的毒性。我们设计方法的目的是产生具有增强的抗微生物效力和针对微生物而非哺乳动物细胞的选择性的新型肽。我们的研究结果表明,共有肽对广泛的革兰氏阳性和革兰氏阴性细菌显示出有效的抗菌活性。我们的膜渗透研究表明,该肽有效地诱导膜损伤,并因此通过细胞裂解过程导致细胞死亡。发现肽的微生物DNA结合测定非常弱,表明肽不靶向微生物DNA。Pepcon在抗微生物浓度下诱导最小的细胞毒性,因为在最小抑制浓度(MIC)下发现溶血活性为零。我们的研究结果表明,共有肽设计策略在产生肽方面是有效的。
The rise of multidrug-resistant bacteria is causing a serious threat to the world\'s human population. Recent reports have identified bacterial strains displaying pan drug resistance against antibiotics and generating fears among medical health specialists that humanity is on the dawn of entering a post-antibiotics era. Global research is currently focused on expanding the lifetime of current antibiotics and the development of new antimicrobial agents to tackle the problem of antimicrobial resistance. In the present study, we designed a novel
consensus peptide named \"Pepcon\" through peptide
consensus sequence determination among members of a highly homologous group of
scorpion antimicrobial peptides. Members of this group were found to possess moderate antimicrobial activity with significant toxicity against mammalian cells. The aim of our design method was to generate a novel peptide with an enhanced antimicrobial potency and selectivity against microbial rather than mammalian cells. The results of our study revealed that the
consensus peptide displayed potent antibacterial activities against a broad range of Gram-positive and Gram-negative bacteria. Our membrane permeation studies displayed that the peptide efficiently induced membrane damage and consequently led to cell death through the process of cell lysis. The microbial DNA binding assay of the peptide was found to be very weak suggesting that the peptide is not targeting the microbial DNA. Pepcon induced minimal cytotoxicity at the antimicrobial concentrations as the hemolytic activity was found to be zero at the minimal inhibitory concentrations (MICs). The results of our study demonstrate that the
consensus peptide design strategy is efficient in generating peptides.