Antibacterial properties of Latarcin 1 derived cell-penetrating peptides
Antibacterial properties of Latarcin 1 derived cell-penetrating peptides
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DOI：
10.1016/j.ejps.2018.01.015
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发表时间：
2018-03-30
影响因子：
4.6
通讯作者：
Chugh, Archana
中科院分区：
文献类型：
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作者：
Budagavi, Deepthi Poornima;Chugh, Archana
细胞穿透肽（CPPs）和抗菌肽（AMPs）具有一定的物理化学参数，如两亲性、疏水性、阳离子性和pI，因此这两类肽也表现出重叠的功能特征。在我们目前的工作中，我们评估了从Latarcin1衍生的细胞穿透肽的抗菌性能。Latarcin衍生肽（LDP）对代表性微生物具有抑菌活性，对耐甲氧西林金黄色葡萄球菌（MRSA）具有抑菌作用，是本文研究的模式生物。然而，LDP对HeLa细胞表现出细胞毒性。此外，将核定位序列（NLS）融合到LDP中，有趣的是，LDP-NLS对细菌有抗菌作用，对MRSA有杀菌作用，并且在最高浓度的HeLa细胞中没有表现出细胞毒性。因此，我们的研究结果推断，NLS与LDP的融合显著降低了LDP对HeLa细胞的细胞毒性（Ponnappan and Chugh, 2017），并且与单独使用LDP相比，在MRSA中表现出更高的细胞穿透活性。摄取试验、时间杀伤试验和PI膜损伤试验的综合结果表明，LDP主要通过膜损伤杀死MRSA，而LDP- nls可能具有细胞内靶点。由于其在HeLa细胞中的细胞穿透活性和对MRSA的抗菌活性，在侵袭实验中观察到LDP-NLS有效地抑制了HeLa细胞内MRSA的感染。因此，我们的研究结果表明，LDPNLS是一种具有AMP和CPP活性的双作用肽，可能是哺乳动物和细菌细胞中肽抗生素和药物传递载体的潜在候选者。
Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) share certain physicochemical parameters such as amphipathicity, hydrophobicity, cationicity and pI, due to which these two groups of peptides also exhibit overlapping functional characteristics. In our current work, we have evaluated antimicrobial properties of cell-penetrating peptides derived from Latarcin1. Latarcin derived peptide (LDP) exhibited antimicrobial activity against representative microorganisms tested and bactericidal effect against methicillin resistant Staphylococcus aureus (MRSA), which was used as model organism of study in the present work. However, LDP exhibited cytotoxicity against HeLa cells. Further, nuclear localization sequence (NLS) was fused to LDP and interestingly, LDP-NLS showed antimicrobial effect against bacteria, showed bactericidal effect against MRSA and also did not exhibit cytotoxicity in HeLa cells till the highest concentrations tested. Thus, our results inferred that fusion of NLS to LDP significantly reduced cytotoxicity of LDP against HeLa cells (Ponnappan and Chugh, 2017) and exhibited significantly higher cell-penetrating activity in MRSA in comparison to LDP alone. Consolidated results of uptake assays, time-kill assays and PI membrane damage assays show that LDP killed MRSA mainly by membrane damage, where as LDP-NLS might have intracellular targets. Owing to its cell-penetrating activity in HeLa cells and antimicrobial activity against MRSA, LDP-NLS efficiently inhibited intracellular infection of MRSA in HeLa cells as observed in invasion assays. Hence, our results suggest that LDPNLS is a dual action peptide with AMP and CPP activity and could be potential candidate as peptide antibiotic and drug delivery vector in both mammalian and bacterial cells.