Laboratory of Physical-Chemical Methods of Investigation and Analysis, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, Russia.
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), 141701 Dolgoprudny, Russia.
Molecules. 2022 Sep 9;27(18):5848. doi: 10.3390/molecules27185848.
Cationic antimicrobial peptides (CAMPs) are considered as next-generation antibiotics with a lower probability of developing bacterial resistance. In view of potential clinical use, studies on CAMP biocompatibility are important. This work aimed to evaluate the behavior of synthetic short CAMPs (designed using bioinformatic analysis of the medicinal leech genome and microbiome) in direct contact with blood cells and plasma. Eight CAMPs were included in the study. Hemolysis and lactate dehydrogenase assays showed that the potency to disrupt erythrocyte, neutrophil and mononuclear cell membranes descended in the order pept_1 > pept_3 ~ pept_5 > pept_2 ~ pept_4. Pept_3 caused both cell lysis and aggregation. Blood plasma and albumin inhibited the CAMP-induced hemolysis. The chemiluminescence method allowed the detection of pept_3-mediated neutrophil activation. In plasma coagulation assays, pept_3 prolonged the activated partial thromboplastin time (APTT) and prothrombin time (at 50 μM by 75% and 320%, respectively). Pept_3 was also capable of causing fibrinogen aggregation. Pept_6 prolonged APTT (at 50 μM by 115%). Pept_2 was found to combine higher bactericidal activity with lower effects on cells and coagulation. Our data emphasize the necessity of investigating CAMP interaction with plasma.
阳离子抗菌肽（CAMPs）被认为是下一代抗生素，其产生细菌耐药性的可能性较低。鉴于其潜在的临床应用，CAMP 生物相容性的研究非常重要。本工作旨在评估合成短 CAMPs（通过对医用水蛭基因组和微生物组的生物信息学分析设计）与血细胞和血浆直接接触时的行为。本研究纳入了 8 种 CAMPs。溶血和乳酸脱氢酶测定表明，破坏红细胞、中性粒细胞和单核细胞的能力依次为 pept_1 > pept_3 ~ pept_5 > pept_2 ~ pept_4。Pept_3 可引起细胞裂解和聚集。血浆和白蛋白抑制 CAMP 诱导的溶血。化学发光法可检测到 pept_3 介导的中性粒细胞激活。在血浆凝血测定中，pept_3 延长了活化部分凝血活酶时间（APTT）和凝血酶原时间（在 50 μM 时分别延长了 75%和 320%）。Pept_3 还可引起纤维蛋白原聚集。Pept_6 延长了 APTT（在 50 μM 时延长了 115%）。发现 pept_2 具有更高的杀菌活性和更低的细胞及凝血作用。我们的数据强调了研究 CAMP 与血浆相互作用的必要性。
