Cai Shasha, Gao Ningyang, Wang Junhan, Li Jing
The Key Laboratory for Medical Functional Nanomaterials, College of Medical Engineering, Jining Medical University, Jining 272067, China.
Biomolecules. 2025 Jun 20;15(7):908. doi: 10.3390/biom15070908.
Regulating the innate immune response against infections, particularly drug-resistant bacteria, is a key focus in anti-infection therapy. Cathelicidins, found in vertebrates, are crucial for pathogen resistance. Few studies have explored gecko cathelicidins' anti-infection properties. Recently, five new cathelicidins (Gj-CATH1-5) were identified in . The peptide Gj-CATH5, from , shows promise against through various mechanisms. This study examined Gj-CATH5's protective effects using in vitro and in vivo models, finding that it significantly reduced bacterial load in a mouse infection model when administered before or shortly after infection. Flow cytometry and the plate counting method showed that Gj-CATH5 boosts neutrophil and macrophage activity, enhancing chemotaxis, phagocytosis, and bactericidal functions. Gj-CATH5 increases ROS production, MPO activity, and NET formation, aiding pathogen clearance. Its amphipathic α-helical structure supports broad-spectrum bactericidal activity (MBC: 4-8 μg/mL) against Gram-negative and antibiotic-resistant bacteria. Gj-CATH5 is minimally cytotoxic (<8% hemolysis at 200 μg/mL) and preserves cell viability at therapeutic levels. These results highlight Gj-CATH5's dual role in pathogen elimination and immune modulation, offering a promising approach to combat multidrug-resistant infections while reducing inflammation. This study enhances the understanding of reptilian cathelicidins and lays the groundwork for peptide-based immune therapies against difficult bacterial infections.
调节针对感染尤其是耐药细菌的先天性免疫反应是抗感染治疗的关键重点。在脊椎动物中发现的cathelicidins对病原体抵抗至关重要。很少有研究探索壁虎cathelicidins的抗感染特性。最近，在……中鉴定出了五种新的cathelicidins（Gj-CATH1-5）。来自……的肽Gj-CATH5通过多种机制显示出对抗……的潜力。本研究使用体外和体内模型检查了Gj-CATH5的保护作用，发现当在感染前或感染后不久给药时，它能显著降低小鼠感染模型中的细菌载量。流式细胞术和平板计数法表明，Gj-CATH5可增强中性粒细胞和巨噬细胞的活性，增强趋化性、吞噬作用和杀菌功能。Gj-CATH5可增加活性氧的产生、髓过氧化物酶活性和中性粒细胞胞外陷阱的形成，有助于病原体清除。其两亲性α-螺旋结构支持对革兰氏阴性菌和耐药菌的广谱杀菌活性（最低杀菌浓度：4-8μg/mL）。Gj-CATH5的细胞毒性极小（在200μg/mL时溶血率<8%），并在治疗水平下保持细胞活力。这些结果突出了Gj-CATH5在病原体清除和免疫调节中的双重作用，为对抗多重耐药感染同时减轻炎症提供了一种有前景的方法。本研究增进了对爬行动物cathelicidins的理解，并为基于肽的针对难治性细菌感染的免疫治疗奠定了基础。
