The lipid components of high-density lipoproteins (HDL) are essential for the binding and transportation of antimicrobial peptides in human serum

• Published in: Scientific reports Vol. 12; no. 1; p. 2576
• Main Authors: Tang, Wen-Hung, Wang, Shi-Han, Wang, Chiu-Feng, Mou, Yun, Lin, Min-Guan, Hsiao, Chwan-Deng, Liao, You-Di
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/337; 631/45; Anti-Bacterial Agents - metabolism; Antimicrobial peptides; Antimicrobial Peptides - metabolism; Bacteria - metabolism; Bacterial diseases; Blood Proteins - metabolism; Cholesterol; High density lipoprotein; Humanities and Social Sciences; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Ionic strength; Lecithin; Lipids - chemistry; Lipoproteins; Lipoproteins, HDL - metabolism; multidisciplinary; Peptides; Phosphatidylcholine; Phospholipids; Science; Science (multidisciplinary); Serum - metabolism; Translocation
• ISSN: 2045-2322; 2045-2322
• 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.