Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils

被引:15
|
作者
Xie, Fang [1 ]
Zan, Yanan [1 ]
Zhang, Xinyuan [1 ,2 ]
Zhang, Huihui [1 ]
Jin, Mingjie [1 ,3 ]
Zhang, Wanjiang [1 ]
Zhang, Yueling [1 ]
Liu, Siguo [1 ]
机构
[1] Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150069, Peoples R China
[2] Inner Mongolia Agr Univ, Coll Vet Med, Hohhot 010000, Peoples R China
[3] Northeast Agr Univ, Coll Vet Med, Harbin 150069, Peoples R China
基金
黑龙江省自然科学基金; 中国国家自然科学基金;
关键词
antimicrobial peptide; cathelicidins; bactericidal activity; antibiofilm; immunomodulation; neutrophils; chemotaxis; extracellular traps; Pseudomonas aeruginosa; ANTIMICROBIAL PEPTIDE LL-37; ANTIBIOTIC-RESISTANCE; STRATEGIES; MECHANISM; CLEAVAGE;
D O I
10.3390/ijms21051871
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mammalian cathelicidins act as the potent microbicidal molecules for controlling bacterial infection, and are considered promising alternatives to traditional antibiotics. Their ability to modulate host immune responses, as well as their bactericidal activities, is essential for therapeutic interventions. In this study, we compared the bactericidal activities, antibiofilm activities and immune-modulatory properties of cathelicidins BMAP-27, BMAP-34, mCRAMP, and LL-37, and evaluated the therapeutic efficacy of the combination of BMAP-27 and LL-37 using a mouse pulmonary infection model. Our results showed that all of the four cathelicidins effectively killed bacteria via rapid induction of membrane permeabilization, and BMAP-27 exhibited the most excellent bactericidal activity against diverse bacterial pathogens. BMAP-27, mCRAMP, and LL-37 effectively inhibited biofilm formation, while BMAP-34, mCRAMP and LL-37 exerted immunomodulatory functions with varying degrees of efficacy by stimulating the chemotaxis of neutrophils, inducing the production of reactive oxygen species, and facilitating the formation of neutrophil extracellular traps. Of note, the combination of BMAP-27 and LL-37 effectively enhanced the clearance of Pseudomonas aeruginosa and reduced the organ injury in vivo. Together, these findings highlight that identifying the appropriate synergistic combination of mammalian cathelicidins with different beneficial properties may be an effective strategy against bacterial infection.
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页数:19
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