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

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 interven...

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Detalles Bibliográficos
Autores principales: Xie, Fang, Zan, Yanan, Zhang, Xinyuan, Zhang, Huihui, Jin, Mingjie, Zhang, Wanjiang, Zhang, Yueling, Liu, Siguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084556/
https://www.ncbi.nlm.nih.gov/pubmed/32182913
http://dx.doi.org/10.3390/ijms21051871
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author Xie, Fang
Zan, Yanan
Zhang, Xinyuan
Zhang, Huihui
Jin, Mingjie
Zhang, Wanjiang
Zhang, Yueling
Liu, Siguo
author_facet Xie, Fang
Zan, Yanan
Zhang, Xinyuan
Zhang, Huihui
Jin, Mingjie
Zhang, Wanjiang
Zhang, Yueling
Liu, Siguo
author_sort Xie, Fang
collection PubMed
description 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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spelling pubmed-70845562020-03-24 Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils Xie, Fang Zan, Yanan Zhang, Xinyuan Zhang, Huihui Jin, Mingjie Zhang, Wanjiang Zhang, Yueling Liu, Siguo Int J Mol Sci Article 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. MDPI 2020-03-09 /pmc/articles/PMC7084556/ /pubmed/32182913 http://dx.doi.org/10.3390/ijms21051871 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xie, Fang
Zan, Yanan
Zhang, Xinyuan
Zhang, Huihui
Jin, Mingjie
Zhang, Wanjiang
Zhang, Yueling
Liu, Siguo
Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
title Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
title_full Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
title_fullStr Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
title_full_unstemmed Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
title_short Differential Abilities of Mammalian Cathelicidins to Inhibit Bacterial Biofilm Formation and Promote Multifaceted Immune Functions of Neutrophils
title_sort differential abilities of mammalian cathelicidins to inhibit bacterial biofilm formation and promote multifaceted immune functions of neutrophils
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084556/
https://www.ncbi.nlm.nih.gov/pubmed/32182913
http://dx.doi.org/10.3390/ijms21051871
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