High throughput in vivo laboratory models is need for screening and identification of effective therapeutic agents to overcome microbial drug-resistance. This study was undertaken to evaluate in vivo antimicrobial efficacy of short-chain antimicrobial peptide- Cecropin A (1–7)-Melittin (CAMA) against three multi-drug resistant enteroaggregative Escherichia coli (MDR-EAEC) field isolates in a Galleria mellonella larval model. The minimum inhibitory concentration (MIC; 2.0 mg/L) and minimum bactericidal concentration (MBC; 4.0 mg/L) of CAMA were determined by microdilution assay. CAMA was found to be stable at high temperatures, physiological concentration of cationic salts and proteases; safe with sheep erythrocytes, secondary cell lines and commensal lactobacilli at lower MICs; and exhibited membrane permeabilization. In vitro time-kill assay revealed concentration- and time-dependent clearance of MDR-EAEC in CAMA-treated groups at 30 min. CAMA- treated G. mellonella larvae exhibited an increased survival rate, reduced MDR-EAEC counts, immunomodulatory effect and proved non-toxic which concurred with histopathological findings. CAMA exhibited either an equal or better efficacy than the tested antibiotic control, meropenem. This study highlights the possibility of G. mellonella larvae as an excellent in vivo model for investigating the host-pathogen interaction, including the efficacy of antimicrobials against MDR-EAEC strains.

中文翻译：

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探索大毒蛾幼虫模型评价天蚕素A（1-7）-蜂毒肽对多重耐药肠聚集性大肠埃希菌的抗菌作用

需要高通量体内实验室模型来筛选和鉴定有效的治疗剂以克服微生物耐药性。本研究旨在评估短链抗菌肽 - Cecropin A (1-7)-Melittin (CAMA) 在大肠埃希氏菌幼虫中对三种多药耐药肠聚集性大肠杆菌 (MDR-EAEC) 现场分离株的体内抗菌功效模型。通过微量稀释法测定CAMA的最低抑菌浓度（MIC；2.0 mg/L）和最低杀菌浓度（MBC；4.0 mg/L）。发现 CAMA 在高温、生理浓度的阳离子盐和蛋白酶下是稳定的；在较低的 MIC 下对绵羊红细胞、次级细胞系和共生乳酸杆菌是安全的；并表现出膜通透性。体外时间杀伤试验揭示了在 30 分钟时 CAMA 治疗组中 MDR-EAEC 的浓度和时间依赖性清除。CAMA 处理的 G. mellonella 幼虫表现出提高的存活率、减少的 MDR-EAEC 计数、免疫调节作用并证明无毒，这与组织病理学发现一致。CAMA 表现出与测试的抗生素对照美罗培南相同或更好的功效。这项研究强调了 G. mellonella 幼虫作为研究宿主-病原体相互作用的优秀体内模型的可能性，包括抗菌剂对 MDR-EAEC 菌株的功效。免疫调节作用并证明无毒，这与组织病理学发现一致。CAMA 表现出与测试的抗生素对照美罗培南相同或更好的功效。这项研究强调了 G. mellonella 幼虫作为研究宿主-病原体相互作用的优秀体内模型的可能性，包括抗菌剂对 MDR-EAEC 菌株的功效。免疫调节作用并证明无毒，这与组织病理学发现一致。CAMA 表现出与测试的抗生素对照美罗培南相同或更好的功效。这项研究强调了 G. mellonella 幼虫作为研究宿主-病原体相互作用的优秀体内模型的可能性，包括抗菌剂对 MDR-EAEC 菌株的功效。