Antimicrobial peptides (AMPs) have gained interesting as a new type of antimicrobial agent. The cathelicidin-derived antimicrobial peptide PMAP-23 has broad-spectrum antibacterial activity, and to improve its antimicrobial activity, we used amino acid substitution at position 5 or 19 of PMAP-23 to design three analogs, named PMAP-23R (Leu⁵--Arg), PMAP-23I (Thr¹⁹--Ile), and PMAP-23RI (Leu⁵--Arg and Thr¹⁹--Ile). We found that the analog peptides exhibited higher stability and improved antibacterial activity compared with PMAP-23. Additionally, the analog peptides PMAP-23I and PMAP-23RI inhibited the growth of Shigella flexneri CICC 21534, whereas PMAP-23 and PMAP-23R exhibited no antibacterial activity against S. flexneri CICC 21534. Moreover, the peptide analogs showed negligible hemolysis and cytotoxicity. We also found that PMAP-23RI exerted impressive therapeutic effects on mice infected with Staphylococcus aureus ATCC 25923 and Salmonella enterica serovar Typhimurium SL1344. PMAP-23RI induced a greater reduction in pathological damage and a higher decrease in the bacterial gene copies in the lung and liver tissues and greatly reduced mouse mortality. In conclusion, the peptide analogs PMAP-23R, PMAP-23I, and PMAP-23RI enhanced the stability and antimicrobial activity of PMAP-23, but PMAP-23RI exhibits more promise as a new antimicrobial agent candidate for the treatment of bacterial infections.

作为一种新型的抗菌剂，抗菌肽（AMPs）引起了人们的兴趣。导管素衍生的抗微生物肽PMAP-23具有广谱的抗菌活性，并提高其抗微生物活性，我们使用了氨基酸取代在位置5或PMAP-23的19到设计了三种类似物，命名PMAP-23R（亮氨酸⁵ - -Arg），PMAP-23I（Thr ¹⁹ -Ile）和PMAP-23RI（Leu ⁵ -Arg和Thr ¹⁹ -Ile）。我们发现，与PMAP-23相比，类似物肽表现出更高的稳定性和改善的抗菌活性。此外，类似物肽PMAP-23I和PMAP-23RI抑制弗氏志贺氏菌的生长CICC 21534，而PMAP-23和PMAP-23R对弗氏链球菌CICC 21534没有表现出抗菌活性。此外，肽类似物的溶血和细胞毒性可忽略不计。我们还发现，PMAP-23RI对金黄色葡萄球菌ATCC 25923和肠炎沙门氏菌感染的小鼠具有令人印象深刻的治疗作用血清鼠伤寒SL1344。PMAP-23RI引起更大程度的病理损伤减少，并且肺和肝组织中细菌基因拷贝的减少程度更高，并大大降低了小鼠的死亡率。总之，肽类似物PMAP-23R，PMAP-23I和PMAP-23RI增强了PMAP-23的稳定性和抗微生物活性，但PMAP-23RI作为治疗细菌感染的新型抗微生物剂候选物表现出更大的希望。