In wake of antimicrobial resistance (AMR), the present study evaluated the antimicrobial efficacy of chitosan-encapsulated Cecropin-A (1–7)-melittin-cell penetrating peptide (ENC CAMA-CPP) against multi-drug-resistant (MDR) Salmonella Enteritidis. The ENC CAMA-CPP synthesized by ionic gelation technique revealed a particle size of 597.5 ± 13.20 nm and zeta potential of 2.80 ± 0.12 mV. The functional groups including encapsulation confirmation and morphology were evident by Fourier transform infrared spectroscopy and scanning electron microscopy, respectively. On HPLC analysis, an encapsulation efficiency of 75.12 ± 1.52% was observed. Further, a pH-dependent sustained release along with a maximum release of 97% was evident at pH ≥ 8.0 up to 120 h. In vitro, ENC CAMA-CPP was found stable against protease enzymes (trypsin and proteinase K) and biological fluids (simulated gastric fluid and simulated intestinal fluid) and was also tested safe for sheep RBCs, mammalian cells, and beneficial lactobacilli. In the in vitro time-kill assay, ENC CAMA-CPP eliminated intracellular MDR S. Enteritidis at 12 h p.i., while in the in vivo Galleria mellonella larvae model, an improved survival rate, reduced bacterial count, with significant (p < 0.001) immunomodulatory effect and minimal cytotoxicity were evident for ENC CAMA-CPP. Overall, ENC CAMA-CPP appears to be a promising therapeutic candidate against MDR S. Enteritidis and warrants further validation in an appropriate animal model.

在出现抗菌素耐药性 (AMR) 之后，本研究评估了壳聚糖包裹的天蚕素-A (1–7)-蜂毒肽-细胞穿透肽 (ENC CAMA-CPP) 对多重耐药 (MDR)沙门氏菌的抗菌功效肠炎。通过离子凝胶技术合成的 ENC CAMA-CPP 显示粒径为 597.5 ± 13.20 nm，zeta 电位为 2.80 ± 0.12 mV。傅里叶变换红外光谱和扫描电子显微镜分别证明了包括封装确认和形态在内的官能团。在 HPLC 分析中，观察到的封装效率为 75.12 ± 1.52%。此外，在 pH ≥ 8.0 长达 120 小时时，pH 依赖性持续释放和 97% 的最大释放是明显的。体外, ENC CAMA-CPP 被发现对蛋白酶（胰蛋白酶和蛋白酶 K）和生物体液（模拟胃液和模拟肠液）稳定，并且还测试了对绵羊红细胞、哺乳动物细胞和有益乳酸杆菌的安全性。在体外时间杀灭试验中，ENC CAMA-CPP 消除了细胞内MDR S。在感染后 12 小时发生肠炎，而在体内大蜡螟幼虫模型中，ENC CAMA-CPP 的存活率提高，细菌数量减少，具有显着的 (p < 0.001) 免疫调节作用和最小的细胞毒性。总的来说，ENC CAMA-CPP 似乎是一种很有前途的抗 MDR 肠炎沙门氏菌的治疗候选药物，需要在适当的动物模型中进一步验证。