Abstract
Antibiotic resistant bacterial strains represent a global health problem with a strong social and economic impact. Thus, there is an urgent need for the development of antibiotics with novel mechanisms of action. There is currently an extensive effort to understand the mode of action of antimicrobial peptides which are considered as one alternative to classical antibiotics. The main advantage of this class of substances, when considering bacterial resistance, is that they rapidly, within minutes, kill bacteria. Antimicrobial peptides can be found in every organism and display a wide spectrum of activity. Hence, the goal is to engineer peptides with an improved therapeutic index, i.e. high efficacy and target specificity. For the rational design of such novel antibiotics it is essential to elucidate the molecular mechanism of action. Biophysical studies have been performed using to a large extent membrane model systems demonstrating that there are distinctive different mechanisms of bacterial killing by antimicrobial peptides. One can distinguish between peptides that permeabilize and/or disrupt the bacterial cell membrane and peptides that translocate through the cell membrane and interact with a cytosolic target. Lantibiotics exhibit specific mechanisms, e.g. binding to lipid II, a precursor of the peptidoglycan layer, either resulting in membrane rupture by pore formation or preventing cell wall biosynthesis. The classical models of membrane perturbation, pore formation and carpet mechanism, are discussed and related to other mechanisms that may lead to membrane dysfunction such as formation of lipid-peptide domains or membrane disruption by formation of non-lamellar phases. Emphasis is on the role of membrane lipid composition in these processes and in the translocation of antimicrobial peptides.
Keywords: amphipaticity, membrane mimetic, pore formation, carpet mechanism, lipid-peptide domains, non-lamellar, combinatorial libraries, sar
Combinatorial Chemistry & High Throughput Screening
Title: Molecular Mechanisms of Membrane Perturbation by Antimicrobial Peptides and the Use of Biophysical Studies in the Design of Novel Peptide Antibiotics
Volume: 8 Issue: 3
Author(s): K. Lohner and S. E. Blondelle
Affiliation:
Keywords: amphipaticity, membrane mimetic, pore formation, carpet mechanism, lipid-peptide domains, non-lamellar, combinatorial libraries, sar
Abstract: Antibiotic resistant bacterial strains represent a global health problem with a strong social and economic impact. Thus, there is an urgent need for the development of antibiotics with novel mechanisms of action. There is currently an extensive effort to understand the mode of action of antimicrobial peptides which are considered as one alternative to classical antibiotics. The main advantage of this class of substances, when considering bacterial resistance, is that they rapidly, within minutes, kill bacteria. Antimicrobial peptides can be found in every organism and display a wide spectrum of activity. Hence, the goal is to engineer peptides with an improved therapeutic index, i.e. high efficacy and target specificity. For the rational design of such novel antibiotics it is essential to elucidate the molecular mechanism of action. Biophysical studies have been performed using to a large extent membrane model systems demonstrating that there are distinctive different mechanisms of bacterial killing by antimicrobial peptides. One can distinguish between peptides that permeabilize and/or disrupt the bacterial cell membrane and peptides that translocate through the cell membrane and interact with a cytosolic target. Lantibiotics exhibit specific mechanisms, e.g. binding to lipid II, a precursor of the peptidoglycan layer, either resulting in membrane rupture by pore formation or preventing cell wall biosynthesis. The classical models of membrane perturbation, pore formation and carpet mechanism, are discussed and related to other mechanisms that may lead to membrane dysfunction such as formation of lipid-peptide domains or membrane disruption by formation of non-lamellar phases. Emphasis is on the role of membrane lipid composition in these processes and in the translocation of antimicrobial peptides.
Export Options
About this article
Cite this article as:
Lohner K. and Blondelle E. S., Molecular Mechanisms of Membrane Perturbation by Antimicrobial Peptides and the Use of Biophysical Studies in the Design of Novel Peptide Antibiotics, Combinatorial Chemistry & High Throughput Screening 2005; 8 (3) . https://dx.doi.org/10.2174/1386207053764576
DOI https://dx.doi.org/10.2174/1386207053764576 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Low-Dose Aspirin-Associated Upper and Mid Gastrointestinal Tract Damage and Gene Polymorphism
Current Pharmaceutical Design Genetic Polymorphisms of Type-1 and Type-2 Inflammatory Cytokines in Ischaemic Stroke
Vascular Disease Prevention (Discontinued) Novel Pharmacologic Approaches to the Management of Sepsis: Targeting the Host Inflammatory Response
Recent Patents on Inflammation & Allergy Drug Discovery Anti-inflammatory Treatment of Acute Coronary Syndromes
Current Pharmaceutical Design Drug Targets in Infections with Other Emerging Viruses: Influenza Viruses, Metapneumovirus and Hantaviruses
Infectious Disorders - Drug Targets Cytochrome P450-Activated Prodrugs: Targeted Drug Delivery
Current Medicinal Chemistry A Promising Future for Peptides in Ophthalmology: Work Effectively and Smartly
Current Medicinal Chemistry A Randomized, Double Blind, Controlled, Dose Dependent Clinical Trial to Evaluate the Efficacy of a Proanthocyanidin Standardized Whole Cranberry (Vaccinium macrocarpon) Powder on Infections of the Urinary Tract
Current Bioactive Compounds The Effects of Zataria Multiflora on Blood Glucose, Lipid Profile and Oxidative Stress Parameters in Adult Mice During Exposure to Bisphenol A
Cardiovascular & Hematological Disorders-Drug Targets Chemical Modifications Designed to Improve Peptide Stability: Incorporation of Non-Natural Amino Acids, Pseudo-Peptide Bonds, and Cyclization
Current Pharmaceutical Design A Review on Rheumatoid Arthritis Interventions and Current Developments
Current Drug Targets Intradialytic Hypertension: An Under-recognized Cardiovascular Risk Factor. What is the Evidence?
Current Hypertension Reviews Aromatherapy and the Central Nerve System (CNS): Therapeutic Mechanism and its Associated Genes
Current Drug Targets Pediatrics for Disability: A Comprehensive Approach to Children with Syndromic Psychomotor Delay
Current Pediatric Reviews Biomarkers Determining Cardiovascular Risk in Patients with Kidney Disease
Current Medicinal Chemistry Pharmacological Targets for the Inhibition of Neurogenic Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents From Nucleic Acids to Drug Discovery: Nucleobases as Emerging Templates for Drug Candidates
Current Medicinal Chemistry State of the Art of Nanobiotechnology Applications in Neglected Diseases
Current Nanoscience Teenage-pregnancies from a Human Life History Viewpoint – an Updated Review with Special Respect to Prevention Strategies
Current Women`s Health Reviews Myocardial Revascularization for the Elderly: Current Options, Role of Off-pump Coronary Artery Bypass Grafting and Outcomes
Current Cardiology Reviews