pMPES: A Modular Peptide Expression System for the Delivery of Antimicrobial Peptides to the Site of Gastrointestinal Infections Using Probiotics.

pMPES: A Modular Peptide Expression System for the Delivery of Antimicrobial Peptides to the Site of Gastrointestinal Infections Using Probiotics.
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DOI:
10.3390/ph9040060
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发表时间:
2016-10-05
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
Kaznessis YN
Kaznessis YN
中科院分区:
其他
文献类型:
--
作者:
Geldart K;Forkus B;McChesney E;McCue M;Kaznessis YN

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抗菌肽是传统抗生素的一种有前途的替代品,但其实用性受到高生产成本和低生物利用度的限制。细菌生产和抗菌肽(AMP)直接在感染部位的交付可能提供一个有效的治疗应用的途径。在本研究中,我们开发了一个载体,可以用于生产和分泌的七个抗菌肽从大肠杆菌MC1061 F'和益生菌E。coli Nissle 1917.载体pMPES(模块化肽表达系统)采用Microcin V(MccV)分泌系统和强大的合成启动子来驱动AMP产生。在此,我们证明了pMPES产生抑制水平的MccV、小球藻菌素L(MccL)、小球藻菌素N(McnN)、肠菌素A(EntA)、肠菌素P(EntP)、Hiracin JM 79(HirJM 79)和肠菌素B(EntB)的能力。据我们所知,这是第一次证明这样一个广泛适用的分泌系统的AMP生产。这种类型的模块化表达系统可以加快急需的抗菌技术的发展。
Antimicrobial peptides are a promising alternative to traditional antibiotics, but their utility is limited by high production costs and poor bioavailability profiles. Bacterial production and delivery of antimicrobial peptides (AMPs) directly at the site of infection may offer a path for effective therapeutic application. In this study, we have developed a vector that can be used for the production and secretion of seven antimicrobial peptides from both Escherichia coli MC1061 F’ and probiotic E. coli Nissle 1917. The vector pMPES (Modular Peptide Expression System) employs the Microcin V (MccV) secretion system and a powerful synthetic promoter to drive AMP production. Herein, we demonstrate the capacity of pMPES to produce inhibitory levels of MccV, Microcin L (MccL), Microcin N (McnN), Enterocin A (EntA), Enterocin P (EntP), Hiracin JM79 (HirJM79) and Enterocin B (EntB). To our knowledge, this is the first demonstration of such a broadly-applicable secretion system for AMP production. This type of modular expression system could expedite the development of sorely needed antimicrobial technologies.