Antibiotics are essential drugs used to treat pathogenic bacteria, but their prolonged use contributes to the development and spread of drug-resistant microorganisms. Antibiotic resistance is a serious challenge and has led to the need for new alternative molecules less prone to bacterial resistance. Antimicrobial peptides (AMPs) have aroused great interest as potential next-generation antibiotics, since they are bioactive small proteins, naturally produced by all living organisms, and representing the first line of defense against fungi, viruses and bacteria. AMPs are commonly classified according to their sources, which are represented by microorganisms, plants and animals, as well as to their secondary structure, their biosynthesis and their mechanism of action. They find application in different fields such as agriculture, food industry and medicine, on which we focused our attention in this review. Particularly, we examined AMP potential applicability in wound healing, skin infections and metabolic syndrome, considering their ability to act as potential Angiotensin-Converting Enzyme I and pancreatic lipase inhibitory peptides as well as antioxidant peptides. Moreover, we argued about the pharmacokinetic and pharmacodynamic approaches to develop new antibiotics, the drug development strategies and the formulation approaches which need to be taken into account in developing clinically suitable AMP applications.

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Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields

With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a “defensin vaccine” as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.

https://www.mdpi.com/1422-0067/23/5/2499/pdf?version=1646185957

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

Today, researchers are looking at new ways to treat severe infections caused by resistance to standard antibiotic therapy. This is quite challenging due to the complex and interdependent relationships involved: the cause of infection-the patient-antimicrobial agents. The sessile biofilm form is essential in research to reduce resistance to very severe infections (such as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter spp). The purpose of this study is to elucidate the mechanisms of the occurrence, maintenance, and suppression of biofilm infections. One form of biofilm suppression is the efficient action of natural antagonists of bacteria-bacteriophages. Bacteriophages effectively penetrate the biofilm's causative cells. They infect those bacterial cells and either destroy them or prevent the infection spreading. In this process, bacteriophages are specific, relatively easy to apply, and harmless to the patient. Antimicrobial peptides (AMPs) support the mechanisms of bacteriophages' action. AMPs could also attack and destroy infectious agents on their own (even on biofilm). AMPs are simple, universal peptide molecules, mainly cationic peptides. Additional AMP research could help develop even more effective treatments of biofilm (bacteriophages, antibiotics, AMPs, nanoparticles). Here, we review recent unconventional agents, such as bacteriophages and AMPs, used for eradication of biofilm, providing an overview of potentially new biofilm treatment strategies.

https://www.mdpi.com/1424-8247/13/10/299/pdf

The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection.

Antimicrobial peptides (AMPs) are constituents of the innate immune system in every kind of living organism. They can act by disrupting the microbial membrane or without affecting membrane stability. Interest in these small peptides stems from the fear of antibiotics and the emergence of microorganisms resistant to antibiotics. Through membrane or metabolic disruption, they defend an organism against invading bacteria, viruses, protozoa, and fungi. High efficacy and specificity, low drug interaction and toxicity, thermostability, solubility in water, and biological diversity suggest their applications in food, medicine, agriculture, animal husbandry, and aquaculture. Nanocarriers can be used to protect, deliver, and improve their bioavailability effectiveness. High cost of production could limit their use. This review summarizes the natural sources, structures, modes of action, and applications of microbial peptides in the food and pharmaceutical industries. Any restrictions on AMPs’ large-scale production are also taken into consideration.

https://www.mdpi.com/2079-6382/11/11/1483/pdf?version=1666786586

An Overview of the Potentialities of Antimicrobial Peptides Derived from Natural Sources

Abstract Background Antimicrobial peptides (AMPs) are a diverse class of molecules that represent a vital part of innate immunity. AMPs are evolutionarily conserved molecules that exhibit structural and functional diversity. They provide a possible solution to the antibiotic-resistance crisis. Main text These small cationic peptides can target bacteria, fungi, and viruses, as well as cancer cells. Their unique action mechanisms, rare antibiotic-resistant variants, broad-spectrum activity, low toxicity, and high specificity encourage pharmaceutical industries to conduct clinical trials to develop them as therapeutic drugs. The rapid development of computer-assisted strategies accelerated the identification of AMPs. The Antimicrobial Peptide Database (APD) so far contains 3324 AMPs from different sources. In addition to their applications in different fields, some AMPs demonstrated the potential to combat COVID-19, and hinder viral infectivity in diverse ways. Conclusions This review provides a brief history of AMPs and their features, including classification, evolution, sources and mechanisms of action, biosynthesis pathway, and identification techniques. Furthermore, their different applications, challenges to clinical applications, and their potential use against COVID-19 are presented. 

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Antimicrobial peptides: features, applications and the potential use against covid-19

Antimicrobial peptides (AMPs) are small sized protein molecules which play a crucial role in host inborn immune framework. AMPs with their specific properties are often considered as a barrier against various harmful foreign particles including bacteria, yeast, fungi and virus. These peptides from different sources exhibit diverse functions and structural features. It exploits the unique property of membrane interaction to destroy target organisms and even cellular components are targeted. However, to combat the emerging resistance towards antibiotics, the use of AMPs as natural drugs has gained importance. Efficiency of these peptides can be enhanced by modification in different aspects through in silico approach. In this article we focus on the areas on antimicrobial peptides like source, properties, classification, mechanism of action, resistance and strategies for its applications.

Ankita Borah

Papers

A Crosstalk on Antimicrobial Peptides