Investigation of the Role of Aromatic Residues in the Antimicrobial Peptide BuCATHL4B.
Investigation of the Role of Aromatic Residues in the Antimicrobial Peptide BuCATHL4B.
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研究芳族残基在抗菌肽bucathl4b中的作用。
DOI：
10.2174/0929866527666200813202918
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发表时间：
2021
影响因子：
1.6
通讯作者：
Caputo GA
中科院分区：
文献类型：
--
作者：
Necelis MR;Santiago-Ortiz LE;Caputo GA
抗菌肽（AMP）是传统小分子抗生素的一种有吸引力的替代品，因为抗菌肽通常靶向细菌细胞膜。buCATHL 4 B是一种来源于布法罗（Bubalus bubalis）的富含Trp的肽序列，是一种广谱抗菌肽。在这项工作中，天然色氨酸残基被替换为其他天然存在的芳香族氨基酸，开始阐明这些残基对肽活性的重要性。最小抑菌浓度（MIC）结果表明对7种细菌菌株的活性。进行膜和双层透化测定以解决双层破坏在肽的活性中的作用。还进行了脂质囊泡结合和淬灭实验，以了解肽如何与脂质双层相互作用。MIC结果表明，原始的富含色氨酸的序列和苯丙氨酸取代的序列表现出对细菌生长的强烈抑制。在透化测定中，具有苯丙氨酸取代的肽比那些被酪氨酸取代的肽具有更高水平的膜透化。此外，两个酪氨酸取代的序列之一，YWY，表现最不同的最低的抗微生物活性，显示没有透化的细菌膜。值得注意的是，抗微生物活性本质上是物种依赖性的，对不同的细菌具有不同的活性水平。膜透化和活性之间似乎几乎没有相关性，表明这些肽可能具有膜破坏以外的其他作用机制。结果还鉴定了两个序列，表示为FFF和YYW，其保留抗菌活性，但具有显著降低的溶血活性。
Antimicrobial peptides (AMPs) are an attractive alternative to traditional small molecule antibiotics as AMPs typically target the bacterial cell membrane. A Trp-rich peptide sequence derived from water buffalo (Bubalus bubalis), buCATHL4B was previously identified as a broad-spectrum antimicrobial peptide. In this work, native Trp residues were replaced with other naturally occurring aromatic amino acids to begin to elucidate the importance of these residues on peptide activity. Minimal inhibitory concentration (MIC) results demonstrated activity against seven strains of bacteria. Membrane and bilayer permeabilization assays were performed to address the role of bilayer disruption in the activity of the peptides. Lipid vesicle binding and quenching experiments were also performed to gain an understanding of how the peptides interacted with lipid bilayers. MIC results indicate the original, tryptophan-rich sequence, and the phenylalanine substituted sequences exhibit strong inhibition of bacterial growth. In permeabilization assays, peptides with phenylalanine substitutions have higher levels of membrane permeabilization than those substituted with tyrosine. In addition, one of the two-tyrosine substituted sequence, YWY, behaves most differently in the lowest antimicrobial activity, showing no permeabilization of bacterial membranes. Notably the antimicrobial activity is inherently species dependent, with varying levels of activity against different bacteria. There appears to be little correlation between membrane permeabilization and activity, indicating these peptides may have additional mechanisms of action beyond membrane disruption. The results also identify two sequences, denoted FFF and YYW, which retain antibacterial activity but have markedly reduced hemolytic activity.
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影响因子：
3.4
作者：
Boopathy, Mani;Selvam, Ramasamy;Subramanian, Kathavarayan
通讯作者：
Subramanian, Kathavarayan
DOI：
10.3390/ph11010003
发表时间：
2018-01-02
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Almaaytah A;Qaoud MT;Khalil Mohammed G;Abualhaijaa A;Knappe D;Hoffmann R;Al-Balas Q
通讯作者：
Al-Balas Q
影响因子：
2.9
作者：
Caputo, GA;London, E
通讯作者：
London, E
影响因子：
4.6
作者：
Gibney, Katherine A.;Sovadinova, Iva;Lopez, Analette I.;Urban, Michael;Ridgway, Zachary;Caputo, Gregory A.;Kuroda, Kenichi
通讯作者：
Kuroda, Kenichi
影响因子：
3.5
作者：
Capilato, Joseph N.;Philippi, Shane V.;Perez, Lark J.
通讯作者：
Perez, Lark J.