Lights and Shadows on the Therapeutic Use of Antimicrobial Peptides

Abstract

The emergence of antimicrobial-resistant infections is still a major concern for public health worldwide. The number of pathogenic microorganisms capable of resisting common therapeutic treatments are constantly increasing, highlighting the need of innovative and more effective drugs. This phenomenon is strictly connected to the rapid metabolism of microorganisms: due to the huge number of mutations that can occur in a relatively short time, a colony can “adapt” to the pharmacological treatment with the evolution of new resistant species. However, the shortage of available antimicrobial drugs in clinical use is also caused by the high costs involved in developing and marketing new drugs without an adequate guarantee of an economic return; therefore, the pharmaceutical companies have reduced their investments in this area. The use of antimicrobial peptides (AMPs) represents a promising strategy for the design of new therapeutic agents. AMPs act as immune defense mediators of the host organism and show a poor ability to induce antimicrobial resistance, coupled with other advantages such as a broad spectrum of activity, not excessive synthetic costs and low toxicity of both the peptide itself and its own metabolites. It is also important to underline that many antimicrobial peptides, due to their inclination to attack cell membranes, have additional biological activities, such as, for example, as anti-cancer drugs. Unfortunately, they usually undergo rapid degradation by proteolytic enzymes and are characterized by poor bioavailability, preventing their extensive clinical use and landing on the pharmaceutical market. This review is focused on the strength and weak points of antimicrobial peptides as therapeutic agents. We give an overview on the AMPs already employed in clinical practice, which are examples of successful strategies aimed at overcoming the main drawbacks of peptide-based drugs. The review deepens the most promising strategies to design modified antimicrobial peptides with higher proteolytic stability with the purpose of giving a comprehensive summary of the commonly employed approaches to evaluate and optimize the peptide potentialities.

Why the Ala-His-His Peptide Is an Appropriate Scaffold to Remove and Redox Silence Copper Ions from the Alzheimer’s-Related Aβ Peptide

“…Here, we make use of a short peptide, namely the Ala-His-His-COOH (AHH), to illustrate why such peptide scaffolds are highly suitable to stop the production of ROS induced by Cu(Aβ). The main drawback of peptides, id est, a weak proteolytic stability [ 26 ], is currently the subject of intense lines of research aimed at overcoming such issues, either by the use of peptidomimetic molecules [ 27 , 28 , 29 ], D-isomers, [ 30 ] or smart delivery systems [ 31 , 32 , 33 , 34 ]. In contrast, peptides have the great advantage of being easily tunable.…”

Antimicrobial peptides originating from expression libraries ofAurelia auritaandMnemiopsis leidyiprevent biofilm formation of opportunistic pathogens

“…P. aeruginosa biofilm formation was only affected by BiP_Aa_5 and BiP_Ml_3 at high concentrations. A common concern around using AMPs as new antimicrobials is their high susceptibility to enzymatic degradation by proteases [10,35]. P. aeruginosa synthesizes many such proteases that are essential virulence factors to interfere with antibacterial defense mechanisms [36], which migth be the reason for our obersvation.…”

Calcitermin-Loaded Smart Gels Activity against Candida albicans: A Preliminary In Vitro Study

“…Despite the improvement of antimicrobial agents, the phenomenon of antimicrobial resistance-the resistance developed by pathogenic microorganisms against previously effective treatments-represents an ever-present clinical and financial burden for the global healthcare system [1,2]. Among several novel approaches devoted to overcoming the global antimicrobial resistance crisis, the use of antimicrobial peptides represents a promising strategy for the design of new drugs [3][4][5][6]. Antimicrobial peptides are phylogenetically ancient biomolecules with a broad spectrum of activity.…”