Design and Characterization of a Novel Hybrid Antimicrobial Peptide OM19R Based on Oncocin and MDAP-2

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Design and Characterization of a Novel Hybrid Antimicrobial Peptide OM19R Based on Oncocin and MDAP‑2 Lei Liu1,2 · Jie Liu1 · Qi Cui1 · Bo‑Yan Jia1 · Zhi‑Hua Pei1 · Kokou Ayefounin Odah1 · Yi‑Ming Wang1 · Wen‑Long Dong1 · Ling‑Cong Kong1 · Hong‑Xia Ma1,3  Accepted: 19 November 2019 © Springer Nature B.V. 2019

Abstract Proline-rich antimicrobial peptides (PR-AMPs) have attracted much interest as they target Gram-negative and do not act by lytic mechanisms. In this study, a novel hybrid peptide OM19R was designed based on the Oncocin and MDAP-2. OM19R showed specific and improved potency against Escherichia coli (E. coli), Salmonella and Shigella standard strains compared to parental peptides. The minimum inhibitory concentrations (MICs) ranged from 1 to 2 μM. However, the activity against Klebsiella pneumoniae (K. pneumoniae) was inhibited. The dependence of the SbmA protein for OM19R activity was also studied by a gene-knockout strain. The confocal laser scanning microscopy further revealed that OM19R could rapidly penetrate into E. coli cells without membrane damage. In summary, the hybrid peptide OM19R is a strong cell-selective antibacterial peptide and a promising specific antibacterial agent. Keywords  Oncocin · MDAP-2 · PR-AMPs · Gram-negative bacteria · SbmA

Introduction In recent years, the overuse of antibiotics has led to increasing bacterial resistance worldwide, especially multidrugresistant bacteria (Khoshnood et al. 2017). Some bacteria that may cause diarrheal among animals and humans, such as E. coli, Salmonella and Shigella were found to be multidrug resistant (Raghunath and Banker 1992). Therefore, Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s1098​9-019-09984​-3) contains supplementary material, which is available to authorized users. * Ling‑Cong Kong [email protected] * Hong‑Xia Ma [email protected] 1



College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street No. 2888, Changchun 130118, Jilin, China

2



School of Medical Laboratory, Jilin Medical University, Jilin Street No.5, Jilin 132013, Jilin, China

3

The Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Xincheng Street No. 2888, Changchun, Jilin, China



development of new and effective therapeutic molecules is of great importance (Lai et al. 2019; Yang et al. 2019). Antimicrobial peptides (AMPs), with unique modes of action against bacteria, have received much attention (Bechinger and Gorr 2017; Lv et al. 2014). However, some limiting factors have hindered their further development, such as AMPs generally strong antimicrobial activities against Gram-positive and Gram-negative bacteria, fungi, and viruses, even including some normal flora in a host organism (Xu et al. 2018). In addition, most of these AMP generally kill bacteria by destroying cell membranes and lead to the spread of potentially harmful toxic components effects the mammalian cellular membranes (Otvos 2002). In