EcDBS1R6: A novel cationic antimicrobial peptide derived from a signal peptide sequence.,Biochimica et Biophysica Acta (BBA) - General Subjects

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EcDBS1R6: A novel cationic antimicrobial peptide derived from a signal peptide sequence.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2020-05-13 , DOI: 10.1016/j.bbagen.2020.129633
William F Porto ₁ , Luz N Irazazabal ₂ , Vincent Humblot ₃ , Evan F Haney ₄ , Suzana M Ribeiro ₅ , Robert E W Hancock ₄ , Ali Ladram ₆ , Octavio L Franco ₇

Affiliation

S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil; Porto Reports, Brasília, DF, Brazil.
Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil; Molecular Pathology Post-graduate Program, University of Brasília, Brasília, Distrito Federal, Brazil.
Sorbonne Université, CNRS, Laboratoire de Réactivité de Surface, LRS, F-75252 Paris, France.
Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall Research Station, Vancouver, British Columbia V6T 1Z4, Canada.
Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal da Grande Dourados, Dourados, MS, Brazil.
Sorbonne Université, CNRS, Institut de Biologie Paris-Seine, IBPS, BIOSIPE, F-75252 Paris, France.
S-Inova Biotech, Pós-graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil; Centro de Análises Proteômicas e Bioquímicas, Pós-Graduação em Ciências Genômicas e Biotecnologia Universidade Católica de Brasília, Brasília, DF, Brazil; Molecular Pathology Post-graduate Program, University of Brasília, Brasília, Distrito Federal, Brazil.

BACKGROUND Bacterial infections represent a major worldwide health problem and the antimicrobial peptides (AMPs) have been considered as potential alternative agents for treating these infections. Here we demonstrated the antimicrobial activity of EcDBS1R6, a peptide derived from a signal peptide sequence of Escherichia coli that we previously turned into an AMP by making changes through the Joker algorithm. METHODS Antimicrobial activity was measured by broth microdilution method. Membrane integrity was measured using fluorescent probes and through scanning electron microscopy imaging. Slide window as used to determine the EcDBS1R6 active core. Molecular dynamics in TFE/water environment was used to assess the EcDBS1R6 structure. RESULTS Signal peptides are known to naturally interact with membranes; however, the modifications introduced by Joker transformed this peptide into membrane-active agent capable of killing bacteria. C-terminus was unable to fold into an α-helix whereas its fragments showed poor or no antimicrobial activity, suggesting that the EcDBS1R6 antibacterial activity core was located at the helical N-terminus, corresponding to the signal peptide portion of the parent peptide. CONCLUSION The strategy of transforming signal peptides into AMPs appears to be promising and could be used to produce novel antimicrobial agents. GENERAL SIGNIFICANCE The process of transforming an inactive signal peptide into an antimicrobial peptide could open a new venue for creating new AMPs derived from signal peptides.

中文翻译：

EcDBS1R6：一种衍生自信号肽序列的新型阳离子抗菌肽。

背景技术细菌感染代表了世界范围内的主要健康问题，并且抗菌肽（AMP）被认为是治疗这些感染的潜在替代药物。在这里，我们展示了EcDBS1R6的抗菌活性，EcDBS1R6是一种来自大肠杆菌信号肽序列的肽，我们之前通过Joker算法进行了更改，从而将其变成了AMP。方法采用肉汤微量稀释法测定其抗菌活性。使用荧光探针和通过扫描电子显微镜成像测量膜的完整性。用于确定EcDBS1R6活动核心的滑动窗口。在TFE /水环境中的分子动力学用于评估EcDBS1R6的结构。结果已知信号肽可与膜天然相互作用。然而，Joker引入的修饰将这种肽转变为能够杀死细菌的膜活性剂。C末端无法折叠成α螺旋，而其片段显示出较弱的抗菌活性或没有抗微生物活性，这表明EcDBS1R6抗菌活性核心位于螺旋N末端，与亲本肽的信号肽部分相对应。结论将信号肽转化为AMP的策略似乎很有希望，可用于生产新型抗菌剂。一般意义将非活性信号肽转化为抗菌肽的过程可能会为创建新的源自信号肽的AMP开辟新的场所。C末端无法折叠成α螺旋，而其片段显示出较弱的抗菌活性或没有抗微生物活性，这表明EcDBS1R6抗菌活性核心位于螺旋N末端，与亲本肽的信号肽部分相对应。结论将信号肽转化为AMP的策略似乎很有希望，可用于生产新型抗菌剂。一般意义将非活性信号肽转化为抗菌肽的过程可能会为创建新的源自信号肽的AMP开辟新的场所。C末端无法折叠成α螺旋，而其片段显示出较弱的抗菌活性或没有抗微生物活性，这表明EcDBS1R6抗菌活性核心位于螺旋N末端，与亲本肽的信号肽部分相对应。结论将信号肽转化为AMP的策略似乎很有希望，可用于生产新型抗菌剂。一般意义将非活性信号肽转化为抗菌肽的过程可能会为创建新的源自信号肽的AMP开辟新的场所。结论将信号肽转化为AMP的策略似乎很有希望，可用于生产新型抗菌剂。一般意义将非活性信号肽转化为抗菌肽的过程可能会为创建新的源自信号肽的AMP开辟新的场所。结论将信号肽转化为AMP的策略似乎很有希望，可用于生产新型抗菌剂。一般意义将非活性信号肽转化为抗菌肽的过程可能会为创建新的源自信号肽的AMP开辟新的场所。

更新日期：2020-05-13

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