Pashaie Fatemeh, Benne Naomi, Holzapfel Philippa I P, Veenendaal Tineke, Bikker Floris J, Heesterbeek Dani A C, Broere Femke, Veldhuizen Edwin J A
Department of Infectious Diseases & Immunology, Division Virology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, the Netherlands.
Department of Medical Microbiology, University Medical Centre Utrecht, 3584 CX, Utrecht, the Netherlands.
Microb Pathog. 2025 Jul;204:107568. doi: 10.1016/j.micpath.2025.107568. Epub 2025 Apr 12.
Antimicrobial peptides (AMPs), such as cathelicidins, show dual functionality by directly combating pathogens and indirectly eliminating them through stimulation of the immune system, generating interest in their therapeutic potential. Pigs have a large set of 11 cathelicidins, of which PMAP-37 is relatively understudied compared to some of the better-known cathelicidins. This study describes the effectiveness of PMAP-37 against both bacteria and viruses. PMAP-37 exhibited potent in vitro antimicrobial activity against both Gram-positive (Bacillus globigii) and Gram-negative bacteria (Escherichia coli) with minimum bactericidal concentrations (MBCs) of 2.5 and 5 μM, respectively. PMAP-37 caused a rapid permeabilization of E. coli's outer and inner membranes within 5 min, indicating its efficacy in disrupting bacterial cell membranes. Furthermore, PMAP-37 neutralized nitric oxide production in a macrophage cell line stimulated with various forms of LPS, Lipid A, or LTA in a dose-dependent manner. Flow cytometric analysis confirmed PMAP-37's capacity to inhibit LPS binding to macrophages, while zeta potential analysis showed the peptide's capacity to neutralize the negative charge of both the E. coli membrane and LPS micellular surfaces. Interestingly, PMAP-37 also exhibited antiviral activity against an important porcine pathogen, the porcine epidemic diarrhea virus (PEDV). These findings underscore the multifunctional properties of PMAP-37, and provide potential leads for future therapeutic use within the pig industry.
抗菌肽（AMPs），如cathelicidins，通过直接对抗病原体和通过刺激免疫系统间接消除病原体而具有双重功能，这使其治疗潜力备受关注。猪有11种cathelicidins，与一些更知名的cathelicidins相比，PMAP - 37的研究相对较少。本研究描述了PMAP - 37对细菌和病毒的有效性。PMAP - 37对革兰氏阳性菌（球状芽孢杆菌）和革兰氏阴性菌（大肠杆菌）均表现出强大的体外抗菌活性，其最低杀菌浓度（MBCs）分别为2.5和5 μM。PMAP - 37在5分钟内使大肠杆菌的外膜和内膜迅速通透，表明其在破坏细菌细胞膜方面的功效。此外，PMAP - 37以剂量依赖的方式中和了用各种形式的脂多糖、脂质A或脂磷壁酸刺激的巨噬细胞系中一氧化氮的产生。流式细胞术分析证实了PMAP - 37抑制脂多糖与巨噬细胞结合的能力，而zeta电位分析表明该肽能够中和大肠杆菌膜和脂多糖微细胞表面的负电荷。有趣的是，PMAP - 37对一种重要的猪病原体——猪流行性腹泻病毒（PEDV）也表现出抗病毒活性。这些发现强调了PMAP - 37的多功能特性，并为未来猪产业的治疗应用提供了潜在线索。
