Bacterial resistance induced by the use of antibiotics has provided a chance for the development of antimicrobial peptides (AMPs), and modification of AMPs to enhance the antibacterial activity or stability has become a research focus. PMAP‐37 is an AMP isolated from porcine myeloid marrow, and studies on its modification have not yet been reported. In this study, three PMAP‐37 analogs named PMAP‐37(F9‐R), PMAP‐37(F34‐R), and PMAP‐37(F9/34‐R) were designed by residue substitution to enhance the positive charge. The antimicrobial activity of PMAP‐37 and its analogs in vitro and in vivo were detected. The results showed that compared with PMAP‐37, PMAP‐37(F9‐R) and PMAP‐37(F9/34‐R) exhibited antibacterial activity against S. flexneri CICC21534. Although PMAP‐37(F34‐R) had no antibacterial activity against S. flexneri CICC21534, its minimal inhibitory concentrations (MICs) were significantly lower than those of PMAP‐37 against most bacterial strains. Besides, all PMAP‐37 analogs were pH stable, retaining stable antibacterial activity after treatment with solution from pH 2 to pH 8/9. In addition, the PMAP‐37 analogs displayed increased thermal stability, and PMAP‐37(F34‐R) retained >60% antibacterial activity after boiling for 2 hours. Furthermore, the PMAP‐37 analogs exhibited impressive therapeutic efficacy in bacterial infections by reducing bacterial burden and inflammatory damage in the lung and liver, resulting in a reduction in mortality. Notably, the therapeutic effect of PMAP‐37(F34‐R) was comparable to that of ceftiofur sodium, and even superior to antibiotics in L. monocytogenes CICC21533 infection model. In conclusion, the PMAP‐37(F34‐R) may be a candidate for the treatment of bacterial infections in the clinic.

中文翻译：

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抗菌肽PMAP-37类似物：增加正电荷以增强PMAP-37的抗菌活性

通过使用抗生素诱导的细菌耐药性为抗菌肽（AMPs）的开发提供了机会，对AMPs进行修饰以增强抗菌活性或稳定性已成为研究的重点。PMAP-37是从猪骨髓提取的AMP，尚未对其修饰进行研究。在这项研究中，通过残基取代设计了三种名为PMAP-37（F9-R），PMAP-37（F34-R）和PMAP-37（F9 / 34-R）的PMAP-37类似物来增强正电荷。检测了PMAP-37及其类似物在体外和体内的抗菌活性。显示的结果表明，与PMAP-37，PMAP-37（F9-R）和PMAP-37（F9 / 34-R）相比表现出抗菌活性对弗氏志贺菌CICC21534。尽管PMAP‐37（F34‐R）对弗氏志贺菌CICC21534，其最小抑菌浓度（MIC）较PMAP-37的抗大多数细菌菌株显著更低。此外，所有PMAP-37类似物均具有pH稳定性，在pH 2至pH 8/9的溶液中处理后仍保持稳定的抗菌活性。此外，PMAP-37类似物显示出更高的热稳定性，煮沸2小时后，PMAP-37（F34-R）保留了60％以上的抗菌活性。此外，PMAP-37类似物通过减少肺部和肝脏中的细菌负担和炎症损害，在细菌感染中显示出令人印象深刻的治疗效果，从而降低了死亡率。值得注意的是，PMAP-37（F34-R）的治疗效果与头孢噻呋钠相当，甚至在单核细胞增生李斯特菌中也优于抗生素。CICC21533感染模型。总之，PMAP-37（F34-R）可能是临床上治疗细菌感染的候选药物。