Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan.
Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan.
Sci Rep. 2022 Feb 16;12(1):2576. doi: 10.1038/s41598-022-06640-7.
Antimicrobial peptides (AMPs) have been developed for the treatment of bacterial infections, but their applications are limited to topical infections since they are sequestered and inhibited in serum. Here we have discovered that the inhibition of AMPs by human serum was mediated through high-density lipoproteins (HDL) which are known to remove cholesterol from peripheral tissues. The susceptibility of AMPs to HDL varied depending on the degree of hydrophobicity of AMPs and their binding affinities to HDL. The phospholipids, such as phosphatidylcholine, of HDL were essential for AMP-binding. The dynamic binding interactions between AMPs and HDL were mediated through the hydrophobic interactions rather than by ionic strength. Interestingly, some AMPs, such as SMAP29, dissociated from the AMP-HDL complex and translocated to bacteria upon contact, while some AMPs, such as LL37, remained in complex with HDL. These results suggest that HDL binds AMPs and facilitates the translocation of them to the bacteria.
抗菌肽 (AMPs) 已被开发用于治疗细菌感染，但由于它们在血清中被隔离和抑制，因此其应用仅限于局部感染。在这里，我们发现人类血清对 AMP 的抑制是通过高密度脂蛋白 (HDL) 介导的，众所周知，HDL 从周围组织中去除胆固醇。AMP 对 HDL 的敏感性取决于 AMP 的疏水性程度及其与 HDL 的结合亲和力。HDL 的磷脂，如磷脂酰胆碱，对于 AMP 结合是必不可少的。AMP 与 HDL 之间的动态结合相互作用是通过疏水性相互作用介导的，而不是通过离子强度。有趣的是，一些 AMP，如 SMAP29，在接触时从 AMP-HDL 复合物中解离并转移到细菌上，而一些 AMP，如 LL37，则与 HDL 保持复合物状态。这些结果表明，HDL 结合 AMP 并促进它们向细菌的转运。
