Prokaryotic Antimicrobial Peptides

The book will provide an overview of the advancement of fundamental knowledge and applications of antimicrobial peptides in biomedical, agricultural, veterinary, food, and cosmetic products. Antimicrobial peptides stand as potentially great alternatives to current antibiotics, and most research in this newly-created area has been published in journals and other periodicals. It is the editors’ opinion that it is timely to sum up the most important achievements in the field and provide the scientific community in a reference book. The goals of this project include illustrating the achievements made so far, debating the state of the art, and drawing new perspectives.

The book will provide an overview of the advancement of fundamental knowledge and applications of antimicrobial peptides in biomedical, agricultural, veterinary, food, and cosmetic products. Antimicrobial peptides stand as potentially great alternatives to current antibiotics, and most research in this newly-created area has been published in journals and other periodicals. It is the editors’ opinion that it is timely to sum up the most important achievements in the field and provide the scientific community in a reference book. The goals of this project include illustrating the achievements made so far, debating the state of the art, and drawing new perspectives.

Antimicrobial Peptides: Challenges and Future Perspectives covers the latest developments about antimicrobial peptides in the scenario of drug resistance. The book is divided into 16 chapters arranged in sequence and preceded by chapters on historical developments and their role as regulatory molecules in innate defense mechanism. Emphasis is given to purification techniques and characterization suitable for interdisciplinary research. Chapters provide an inventory of various antimicrobial peptides, from a diverse array of organisms such as bacteria, fungi, insects, amphibians, plants and mammals. A section on marine ecosystem broadens readers understanding on marine based antimicrobial peptides. Additional sections provide an informative overview on peptides with antiviral properties and those targeting multi-drug resistant bacteria. Recent reports and mechanism on resistance against antimicrobial peptides are also provided, along with key insights into the challenges and future perspectives of peptide drug development. Emphasizes antimicrobial peptides targeting various human viruses and multidrug resistant bacteria Written by internationally recognized experts who provide readers with a wide and useful perspective Provides in-depth resources for undertaking a research work in antimicrobial peptides with the inclusion of chapters on purification techniques and structural details Addresses the possibility and availability of peptide antibiotics in the global drug market Serves as a complete resource from the discovery to drug development of peptide antibiotics

In this text, the small team of expert authors presents the field in a comprehensive and accessible manner that is well suited for students and junior researchers. The result is a highly readable and systematically structured introduction to antimicrobial peptides, their structure, biological function and mode of action. The authors point the way towards a rational design of this potentially highly effective new class of clinical antibiotics on the brink of industrial application. They do this by discussing their design principles, target membranes and structure-activity relationships. The final part of the book describes recent successes in the application of peptides as anticancer agents.

This book presents an overview of antimicrobial peptides (AMPs), their mechanisms of antimicrobial action, other activities, and various problems that must still be overcome regarding their clinical application. Divided into four major parts, the book begins with a general overview of AMPs (Part I), and subsequently discusses the various mechanisms of antimicrobial action and methods for researching them (Part 2). It then addresses a range of activities other than antimicrobial action, such as cell penetration, antisepsis, anticancer, and immunomodulatory activities (Part 3), and explores the prospects of clinical application from various standpoints such as the selective toxicity, design, and discovery of AMPs (Part 4). A huge number of AMPs have been discovered in plants, insects, and vertebrates including humans, and constitute host defense systems against invading pathogenic microorganisms. Consequently, many attempts have been made to utilize AMPs as antibiotics. AMPs could help to solve the urgent problem of drug-resistant bacteria, and are also promising with regard to sepsis and cancer therapy. Gathering a wealth of information, this book will be a bible for all those seeking to develop antibiotics, anti-sepsis, or anticancer agents based on AMPs.

Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.