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Antibiofilm activity of host defence peptides: complexity provides opportunities. ​

文献信息 ​

DOI10.1038/s41579-021-00585-w
PMID34183822
期刊Nature reviews. Microbiology
影响因子103.3
JCR 分区Q1
发表年份2021
被引次数101
关键词宿主防御肽, 抗生物膜活性, 抗菌疗法, 免疫调节
文献类型Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN1740-1526
页码786-797
期号19(12)
作者Robert E W Hancock, Morgan A Alford, Evan F Haney

一句话小结 ​

宿主防御肽（HDPs）是生物体固有免疫的重要成分，具有抗菌、抗生物膜、抗病毒和免疫调节等多种功能，这为抗菌疗法的发展提供了新机会。本文探讨了HDPs的复杂功能及其在治疗药物转化中的挑战，为未来抗生物膜特性药物的研发指明了方向。

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宿主防御肽 · 抗生物膜活性 · 抗菌疗法 · 免疫调节

摘要 ​

宿主防御肽（HDPs）是所有生物体固有免疫的重要组成部分。这些肽可以直接对抗细菌，针对浮游细胞（称为抗菌肽），并展现出抗生物膜（称为抗生物膜肽）、抗病毒、抗真菌以及宿主定向免疫调节等多种活性。在本综述中，我们讨论了HDPs复杂的功能特征如何为抗菌疗法的发展提供了许多机会，特别关注其新兴的抗生物膜特性。我们比较和对比了抗生物膜肽的作用机制与抗菌肽的作用机制。此外，讨论了将候选肽实际转化为治疗药物时面临的障碍及潜在解决方案。值得注意的是，HDPs具备复杂的功能特性，特别是抗生物膜和抗炎活性，以及与传统抗生素的协同作用，这些都赋予了它们额外的价值。

英文摘要 ​

Host defence peptides (HDPs) are integral components of innate immunity across all living organisms. These peptides can exert direct antibacterial effects, targeting planktonic cells (referred to as antimicrobial peptides), and exhibit antibiofilm (referred to as antibiofilm peptides), antiviral, antifungal and host-directed immunomodulatory activities. In this Review, we discuss how the complex functional attributes of HDPs provide many opportunities for the development of antimicrobial therapeutics, focusing particularly on their emerging antibiofilm properties. The mechanisms of action of antibiofilm peptides are compared and contrasted with those of antimicrobial peptides. Furthermore, obstacles for the practical translation of candidate peptides into therapeutics and the potential solutions are discussed. Critically, HDPs have the value-added assets of complex functional attributes, particularly antibiofilm and anti-inflammatory activities and their synergy with conventional antibiotics.

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主要研究问题 ​

  1. 如何评估宿主防御肽的抗生物膜活性与其抗菌活性之间的关系？
  2. 除了抗生物膜活性，宿主防御肽在其他抗微生物应用中有哪些潜在优势？
  3. 在宿主防御肽的临床应用中，存在哪些主要的挑战和障碍？
  4. 如何优化宿主防御肽的设计，以增强其抗生物膜的效果？
  5. 宿主防御肽与传统抗生素的协同作用机制是怎样的，能否提供具体的实例？

核心洞察 ​

1. 研究背景和目的 ​

宿主防御肽（HDPs）是所有生物体固有免疫系统的重要组成部分，具有直接的抗菌效果，能够靶向游离细胞。近年来，随着耐药性细菌的增加，开发新型抗微生物治疗方法变得尤为重要。本研究的目的是探讨HDPs的复杂功能特性，尤其是其抗生物膜（antibiofilm）属性，以寻找新型抗微生物药物的开发机会。

2. 主要方法和发现 ​

本文综述了HDPs的多种功能，包括抗细菌、抗病毒、抗真菌和免疫调节等。研究比较了抗生物膜肽和抗微生物肽的作用机制，探讨了HDPs在实际应用中的挑战，如转化为临床药物的障碍，以及如何克服这些障碍。发现HDPs不仅具有直接的抗菌活性，还具备抗生物膜和抗炎活性，并且与传统抗生素之间存在协同作用，这为其在抗微生物治疗中的应用提供了新的思路。

3. 核心结论 ​

研究表明，宿主防御肽的复杂功能属性为新型抗微生物药物的开发提供了丰富的机会。特别是其抗生物膜特性使其在治疗生物膜相关感染中具有潜力。HDPs的多重作用机制和与传统抗生素的协同效应，使其成为应对抗药性菌株的有力工具。

4. 研究意义和影响 ​

本研究的意义在于强调了宿主防御肽在抗微生物治疗中的多样化应用潜力，尤其是在抗生物膜相关感染领域。通过深入理解HDPs的功能特性和机制，可为新药开发提供新的方向，推动抗生素替代品的研究，最终改善感染性疾病的治疗效果和患者预后。此外，这项研究也为未来的临床应用提供了理论基础，可能改变当前抗微生物治疗的格局，减缓耐药性问题的加剧。

参考文献 ​

  1. The expanding scope of antimicrobial peptide structures and their modes of action. - Leonard T Nguyen;Evan F Haney;Hans J Vogel - Trends in biotechnology (2011)
  2. The value of antimicrobial peptides in the age of resistance. - Maria Magana;Muthuirulan Pushpanathan;Ana L Santos;Leon Leanse;Michael Fernandez;Anastasios Ioannidis;Marc A Giulianotti;Yiorgos Apidianakis;Steven Bradfute;Andrew L Ferguson;Artem Cherkasov;Mohamed N Seleem;Clemencia Pinilla;Cesar de la Fuente-Nunez;Themis Lazaridis;Tianhong Dai;Richard A Houghten;Robert E W Hancock;George P Tegos - The Lancet. Infectious diseases (2020)
  3. The immunology of host defence peptides: beyond antimicrobial activity. - Robert E W Hancock;Evan F Haney;Erin E Gill - Nature reviews. Immunology (2016)
  4. Reassessing the Host Defense Peptide Landscape. - Evan F Haney;Suzana K Straus;Robert E W Hancock - Frontiers in chemistry (2019)
  5. The challenge of antimicrobial resistance: What economics can contribute. - Laurence S J Roope;Richard D Smith;Koen B Pouwels;James Buchanan;Lucy Abel;Peter Eibich;Christopher C Butler;Pui San Tan;A Sarah Walker;Julie V Robotham;Sarah Wordsworth - Science (New York, N.Y.) (2019)
  6. Antimicrobial host defence peptides: functions and clinical potential. - Neeloffer Mookherjee;Marilyn A Anderson;Henk P Haagsman;Donald J Davidson - Nature reviews. Drug discovery (2020)
  7. Strategic approaches to optimizing peptide ADME properties. - Li Di - The AAPS journal (2015)
  8. Immune modulation by multifaceted cationic host defense (antimicrobial) peptides. - Ashley L Hilchie;Kelli Wuerth;Robert E W Hancock - Nature chemical biology (2013)
  9. Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit macromolecular synthesis in Escherichia coli. - Aleksander Patrzykat;Carol L Friedrich;Lijuan Zhang;Valentina Mendoza;Robert E W Hancock - Antimicrobial agents and chemotherapy (2002)
  10. Combined systems approaches reveal highly plastic responses to antimicrobial peptide challenge in Escherichia coli. - Justyna Kozlowska;Louic S Vermeer;Geraint B Rogers;Nabila Rehnnuma;Sarah-Beth T A Amos;Garrit Koller;Michael McArthur;Kenneth D Bruce;A James Mason - PLoS pathogens (2014)

引用本文的文献 ​

  1. Synergy between Indoloquinolines and Ciprofloxacin: An Antibiofilm Strategy against Pseudomonas aeruginosa. - Emilie Charpentier;Ludovic Doudet;Ingrid Allart-Simon;Marius Colin;Sophie C Gangloff;Stéphane Gérard;Fany Reffuveille - Antibiotics (Basel, Switzerland) (2021)
  2. Bacillus amyloliquefaciens-Derived Lipopeptide Biosurfactants Inhibit Biofilm Formation and Expression of Biofilm-Related Genes of Staphylococcus aureus. - Karolína Englerová;Zdenka Bedlovičová;Radomíra Nemcová;Ján Király;Marián Maďar;Vanda Hajdučková;Eva Styková;Rastislav Mucha;Katarína Reiffová - Antibiotics (Basel, Switzerland) (2021)
  3. Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities. - He-Nan Guo;Yu-Cui Tong;Hui-Li Wang;Jing Zhang;Zhong-Xuan Li;Zaheer Abbas;Tian-Tian Yang;Meng-Yao Liu;Pei-Yao Chen;Zheng-Chang Hua;Xiao-Na Yan;Qiang Cheng;Marhaba Ahmat;Jun-Yong Wang;Lu-Lu Zhang;Xu-Biao Wei;Xiu-Dong Liao;Ri-Jun Zhang - International journal of molecular sciences (2021)
  4. Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant Acinetobacter baumannii Infection. - Manigandan Krishnan;Joonhyeok Choi;Ahjin Jang;Young Kyung Yoon;Yangmee Kim - International journal of molecular sciences (2021)
  5. Host Defense Peptide-Mimicking Polymers and Polymeric-Brush-Tethered Host Defense Peptides: Recent Developments, Limitations, and Potential Success. - Hashem Etayash;Robert E W Hancock - Pharmaceutics (2021)
  6. Facile Biofilm Penetration of Cationic Liposomes Loaded with DNase I/Proteinase K to Eradicate Cutibacterium acnes for Treating Cutaneous and Catheter Infections. - Jia-You Fang;Wei-Ling Chou;Chwan-Fwu Lin;Calvin T Sung;Ahmed Alalaiwe;Shih-Chun Yang - International journal of nanomedicine (2021)
  7. AMPing Up the Search: A Structural and Functional Repository of Antimicrobial Peptides for Biofilm Studies, and a Case Study of Its Application to Corynebacterium striatum, an Emerging Pathogen. - Shreeya Mhade;Stutee Panse;Gandhar Tendulkar;Rohit Awate;Yatindrapravanan Narasimhan;Snehal Kadam;Ragothaman M Yennamalli;Karishma S Kaushik - Frontiers in cellular and infection microbiology (2021)
  8. Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms. - Tania Vanzolini;Michela Bruschi;Andrea C Rinaldi;Mauro Magnani;Alessandra Fraternale - International journal of molecular sciences (2022)
  9. Identification of Distinct Characteristics of Antibiofilm Peptides and Prospection of Diverse Sources for Efficacious Sequences. - Bipasa Bose;Taylor Downey;Anand K Ramasubramanian;David C Anastasiu - Frontiers in microbiology (2021)
  10. Isothiazolone-Nitroxide Hybrids with Activity against Antibiotic-Resistant Staphylococcus aureus Biofilms. - Anthony D Verderosa;Sophia Hawas;Jessica Harris;Makrina Totsika;Kathryn E Fairfull-Smith - ACS omega (2022)

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