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

Literature Information ​

DOI10.1038/s41579-021-00585-w
PMID34183822
JournalNature reviews. Microbiology
Impact Factor103.3
JCR QuartileQ1
Publication Year2021
Times Cited101
KeywordsHost Defence Peptides, Antibiofilm Activity, Antimicrobial Therapeutics
Literature TypeJournal Article, Research Support, Non-U.S. Gov't, Review
ISSN1740-1526
Pages786-797
Issue19(12)
AuthorsRobert E W Hancock, Morgan A Alford, Evan F Haney

TL;DR ​

This review highlights the significance of host defence peptides (HDPs) in innate immunity, emphasizing their multifunctional roles, particularly their antibiofilm properties alongside traditional antimicrobial effects. By comparing the mechanisms of action of HDPs and addressing challenges in translating these peptides into effective therapeutics, the study underscores their potential to enhance antimicrobial treatments and combat biofilm-related infections.

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Host Defence Peptides · Antibiofilm Activity · Antimicrobial Therapeutics

Abstract ​

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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Primary Questions Addressed ​

  1. What are the specific mechanisms by which host defence peptides inhibit biofilm formation in various pathogens?
  2. How do the antibiofilm properties of host defence peptides compare to traditional antibiotics in terms of efficacy and resistance?
  3. What potential applications exist for the therapeutic use of host defence peptides in treating biofilm-related infections?
  4. In what ways can the complex functional attributes of host defence peptides be optimized for better antimicrobial therapeutic development?
  5. What are the current challenges in translating the antibiofilm activities of host defence peptides into clinical therapies, and how might these be addressed?

Key Findings ​

1. Research Background and Purpose: Host defence peptides (HDPs) are crucial elements of the innate immune system found across various organisms. They play a significant role in the defense against a wide range of pathogens, including bacteria, viruses, and fungi. Traditional antimicrobial peptides primarily target free-floating (planktonic) cells, but recent insights have highlighted the importance of HDPs in addressing biofilms—aggregated clusters of microorganisms that are resistant to conventional treatments. This review aims to explore the multifaceted roles of HDPs, particularly their antibiofilm activities, and to discuss the implications of these properties for the development of new antimicrobial therapeutics.

2. Main Methods and Findings: The review synthesizes existing literature on the mechanisms of action of HDPs, differentiating between their antimicrobial and antibiofilm activities. It highlights that while antimicrobial peptides primarily disrupt bacterial membranes and inhibit cell growth, antibiofilm peptides engage in more complex interactions that can disrupt biofilm formation, enhance biofilm dispersal, and modulate host immune responses. The review also identifies challenges in translating these promising peptides into effective therapeutic agents, including issues related to stability, toxicity, and delivery methods. Potential solutions to these obstacles, such as peptide modifications and combination therapies with conventional antibiotics, are proposed.

3. Core Conclusions: The findings underscore that the complexity of HDPs provides significant opportunities for the development of innovative antimicrobial therapies. The unique properties of antibiofilm peptides, alongside their ability to synergize with traditional antibiotics, suggest a promising avenue for combating biofilm-related infections that are notoriously difficult to treat. By leveraging the multifaceted actions of HDPs, researchers can potentially overcome some of the limitations posed by conventional antimicrobial agents.

4. Research Significance and Impact: This review highlights the critical role of HDPs in innate immunity and their potential in addressing the growing challenge of antibiotic resistance, particularly in biofilm-associated infections. The insights offered could pave the way for the design of novel therapeutic strategies that utilize the inherent complexities of HDPs. Given the increasing prevalence of chronic infections related to biofilms, this research holds significant implications for public health and the future of antimicrobial drug development, emphasizing the need for continued exploration of HDPs as a viable solution in the fight against resistant pathogens.

References ​

  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)

Literatures Citing This Work ​

  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)

... (91 more literatures)

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