本项目在课题组专抗G−、广谱性抗菌肽研究前期工作基础上，应用细胞学、分子生物学和免疫学技术从细胞、分子水平研究“非剪切嵌合肽”和“剪切嵌合肽”对畜禽腹泻G−致病菌的杀菌、中和LPS及抑制炎症及其相关机制，研究内容：1）基于“linker基因工程”技术联合应用LBP-14、非剪切linker和专抗G−抗菌肽（N2/N6）设计新型高效、低毒多功能“非剪切嵌合肽”，并明确其对畜禽肠道致病菌大肠杆菌的精准靶向杀菌、中和LPS及阻断炎症功能；2）研究由LBP-14、剪切linker和广谱抗菌肽（Lfcin4/Lfcin5）组装的“剪切嵌合肽”对畜禽肠道致病菌沙门氏菌“菌毒并治”的效能；3）初步阐明“非剪切嵌合肽”和“剪切嵌合肽”中和畜禽腹泻致病菌G− LPS的分子机制及抑制炎症反应的分子机制。这为设计新型多功能嵌合肽提供了重要的理论依据，也为畜禽肠道细菌性疾病的多位点协同防控另辟途径。

The strategies of mulfunctional chimeric peptides with different linkers based on “bacterium-toxin symphysial therapy” to control livestock and poultry bacterial diarrhea will be focused on the following three aspects: 1) design of the novel non-cleavable chimeric peptides (LBP-linker-N2/N6) based on LBP-14, flexible or rigid linker and AMP (N2/N6), and evaluation of its stability and resistance, bactericidal activity against Escherichia coli, ability to neutralize LPS and inhibit inflammation in vitro and in vivo; 2) elucidation of the anti-bacterial, anti-toxic, and anti-inflammatory properties of cleavable chimeric peptides (LBP-linker-Lfcin4/Lfcin5) with a cleavable linker against Salmonella enteritidis in vivo; 3) explanation the molecular mechanism of these chimeric peptides with low bacterial resistance, including their interactions with LPS and modulation inflammatory responses. This provides a new idea for the design and development mulfuntional chimeric peptides to fight the gram-negative bacterial infection via multiple target sites in livestock and poultry.