目的 筛选犬皮肤源多药耐药菌，同时基于犬防御素设计衍生肽并探究其抗菌作用。 方法 通过K-B药敏纸片法对临床分离的菌株进行筛选，随后以犬β-防御素3（cBD3）的氨基酸序列为模板，采用氨基酸替换的方式对序列进行设计，选取优化肽cBD3-ABU进行化学合成，利用微量肉汤稀释法检测cBD3-ABU对多药耐药菌的抑菌活性。 结果 筛选获得8株犬皮肤源多药耐药菌；通过固相合成法获得纯度达95.61%的cBD3-ABU；cBD3对大肠杆菌、表皮葡萄球菌、伪中间型葡萄球菌和金黄色葡萄球菌的最小抑菌浓度分别为32、64、64、128 μg/mL，高浓度cBD3-ABU对犬皮肤源大肠杆菌、表皮葡萄球菌、伪中间型葡萄球菌、金黄色葡萄球菌的抑菌率分别为96.02%、81.85%、87.25%、98.91%。 结论 cBD3-ABU在体外具有良好的抑菌活性，具有进一步开发为治疗性药物的潜力。

Objectives The multidrug resistant bacteria from canine skin were screened. The derivative peptide based on canine β-defensin-3 (cBD3) was designed and its antibacterial activity was studied. Methods The clinically isolated strains were screened with K-B drug-sensitive disk method. Subsequently, the amino acid sequence of β-defensin-3 (cBD3) was used as a template to design the sequence with amino acid substitution. The optimized peptide cBD3-ABU was selected for chemical synthesis. The antimicrobial activity of cBD3-ABU against multidrug resistant bacteria was detected with broth microdilution method. Results 8 strains of multidrug resistant bacteria from canine skin were obtained through screening. CBD3-ABU with a purity of 95.61% was obtained through solid-phase synthesis. The minimum inhibitory concentration (MIC) of cBD3 against Escherichia coli, S.epidermidis, S.pseudintermedius, and S.aureus was 32, 64, 64, 128 μg/mL, respectively. The antibacterial rate of high concentration cBD3-ABU against Escherichia coli, Staphylococcus epidermidis, Staphylococcus pseudointermedius and Staphylococcusaureus from canine skin was 96.02%, 81.85%, 87.25%, and 98.91%, respectively. Conclusions CBD3-ABU has good antibacterial activity in vitro and has the potential to be further developed into therapeutic drugs.