Structure-Activity Relationships of the Bacteriocin Bactofencin A and Its Interaction with the Bacterial Membrane.,ACS Infectious Diseases

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Structure-Activity Relationships of the Bacteriocin Bactofencin A and Its Interaction with the Bacterial Membrane.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-12-24 , DOI: 10.1021/acsinfecdis.8b00204
François Bédard _{1,

2} , Ismail Fliss ₃ , Eric Biron _{1,

2}

Affiliation

The antimicrobial peptide bactofencin A is an unmodified non-pediocin-like bacteriocin that inhibits several clinically relevant pathogens, including Listeria monocytogenes and Staphylococcus aureus. Here we report the synthesis and structure-activity relationship studies of bactofencin A and novel analogues thereof. Synthetic bactofencin A was a potent inhibitor of L. monocytogenes (MIC = 8.0 μM) and S. aureus (MIC = 4.0 μM), similar to the bacteriocin produced naturally by Lactobacillus salivarius. Of particular interest is the fact that linear analogues lacking the disulfide bond found in bactofencin A were as potent and also active against several strains of methicillin-resistant S. aureus (MRSA) and one strain of vancomycin-resistant S. aureus (VRSA). Supported by the structure-activity relationship study, investigation of the interaction of bactofencin A with bacterial membrane by molecular dynamics simulations showed the importance of the positively charged N-terminal tail for peptide-membrane interaction. These results suggest that the C-terminal macrocycle is involved in target protein binding and bacterial growth inhibition.

中文翻译：

细菌素Bactofencin A的结构-活性关系及其与细菌膜的相互作用。

抗菌肽bactofencin A是一种未经修饰的非pediocin样细菌素，可抑制几种临床相关病原体，包括单核细胞增生李斯特菌和金黄色葡萄球菌。在这里，我们报告细菌素A及其新型类似物的合成与构效关系的研究。合成的细菌防御素A是单核细胞增生李斯特氏菌（MIC = 8.0μM）和金黄色葡萄球菌（MIC = 4.0μM）的有效抑制剂，类似于唾液乳杆菌自然产生的细菌素。特别令人感兴趣的事实是，缺乏在杆菌素A中发现的二硫键的线性类似物同样有效，并且对几种耐甲氧西林的金黄色葡萄球菌（MRSA）和耐万古霉素的金黄色葡萄球菌（VRSA）都具有活性。在结构-活动关系研究的支持下，通过分子动力学模拟研究bactofencin A与细菌膜的相互作用，发现带正电荷的N末端尾巴对于肽-膜相互作用的重要性。这些结果表明，C末端大环与靶蛋白结合和细菌生长抑制有关。

更新日期：2018-12-12

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