Peptide-Based Antimicrobials: What Is New? Biological Sources and Scaffolds, Production Platforms, Modes of Action, Mechanism of Resistance and Applications

Dear Colleagues,

Antimicrobial resistance (AMR) has emerged as one of the most serious global public health threats of the 21st century and is often referred to as the “silent pandemic”. Unlike acute outbreaks, AMR progresses gradually and largely unnoticed, yet its impact is profound. The continued emergence and spread of resistant pathogens compromise the effectiveness of antibiotics that form the foundation of modern medicine. Routine surgeries, organ transplantation, cancer chemotherapy, intensive care, joint replacement, neonatal care and the management of chronic diseases all depend on the availability of effective antibiotics. Without reliable antimicrobial prophylaxis and treatment, the risk of postoperative infections, sepsis and treatment-related complications increases dramatically. In response to this challenge, significant efforts are being directed toward the development of novel antimicrobial therapies combined with the repurposing of already discovered bioactive molecules. Among the most promising candidates are peptide-based scaffolds, which include already known microbial-sourced antibiotic classes (i.e., glycopeptides, lantibiotics, thiopeptides, etc.) and antimicrobial peptides, which are naturally occurring molecules found in virtually all forms of life as part of the innate immune system. In this Special Issue, we aim to bring together contributions covering the entire spectrum of peptide-based antimicrobials, from naturally occurring antimicrobial peptides to clinically established peptide-derived antibiotics. We particularly welcome studies focused on the discovery and characterization of new peptide molecules from microbial, plant, animal and marine sources, as well as investigations into genome mining, synthetic biology and bioinformatic approaches for identifying novel antimicrobial scaffolds. Contributions addressing production strategies—including native and heterologous expression systems, fermentation optimization, chemical synthesis, semisynthesis and peptide engineering—are also encouraged.

Special attention will be devoted to studies investigating the mechanisms of action of peptide-based antimicrobials, including target identification, membrane disruption, intracellular targets, immunomodulatory effects and resistance evasion mechanisms. We also welcome research exploring combination therapies in which peptides act as antibiotic adjuvants, resistance breakers, membrane permeabilizers or biofilm-disrupting agents capable of restoring susceptibility to conventional antibiotics.

Furthermore, this Special Issue seeks contributions addressing the translational and application-oriented aspects of peptide-based antimicrobials. Topics of interest include the treatment of multidrug-resistant bacterial infections, anti-biofilm strategies, topical and systemic therapeutic applications, antimicrobial coatings for medical devices, implant-associated infection prevention, wound healing, drug delivery systems and peptide-functionalized biomaterials.

Prof. Dr. Flavia Marinelli
Guest Editor

Dr. Matteo Calcagnile
Dr. Francesca Berini
Co-Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Publisher’s Notice

Following discussions between the Antibiotics editorial office and the Guest Editor, two new Guest Editors, Dr. Matteo Calcagnile and Dr. Francesca Berini, have been added to the Special Issue. This change has been approved by the journal Editorial Board, and the Special Issue website has been updated accordingly on 23 July 2026. The Special Issue will continue to be handled by the new Guest Editor team in accordance with MDPI’s Special Issue and editorial policies.

• antimicrobial peptides
• antibiotics
• thiopeptides
• glycopeptides
• lantibiotics
• antimicrobial resistance
• antibiotic adjuvants
• microbial platforms
• topical and systemic infections
• antimicrobial coatings