Single-Gene Encoded and Non-Ribosomal Template Drug-Candidate Antimicrobial Peptides

There has been an endless “war” between pathogen organisms armed with the ability to establish new, genetically based resistance mechanisms, and molecules of antibiotic potential produced (either by Nature or Science) to overcome them. The scientific challenge is to end the permanent danger of epidemics of communicable diseases soon. But the trend is the opposite: the speed of emergence of new Multi Drug Resistant (MDR), Extreme Multi Drug Resistant (XDR), and Pan Drug Resistant (PDR) bacterial pathogens, and eukaryotic parasite strains, including “ESKAPE” species, is higher than that of the appearance of new antibiotics on the market. The search for antibiotic molecules with a novel mode of action is alarming. Antimicrobial peptides (AMPs), due to their large molecular heterogeneity and structural flexibility, provide an alternative, comprising arsenal for overcoming sophisticated resistance mechanisms. We intend to enlarge this arsenal by discovering AMPs with novel mechanisms of action on targeted bugs.

The goal of this Research Topic is to contribute to the international research efforts to discover new anti-multidrug resistance drug candidate peptides applicable in clinical and veterinary medicine (as well as in plant pathology) to overcome multidrug-resistant bacterial pathogens and epidemics caused by them. AMPs, as natural host defense molecules, provide an inexhaustible source of new anti-multidrug resistance peptide drugs, devoted to bacterial membranes, while sparing human (eukaryotic) membranes. (Antiparasitic drugs are another category.) Methodologies allowing the rational exploration of novel structures are available. The history of a drug-candidate AMP-family typically begins with isolation, structural identification of an antibiotic-active natural peptide, followed by bioassays on various targets, determination of physicochemical properties (amino acid sequence, conformation, amphipathic, hydrophobic characters), and determination of its mode of biological actions, accomplished by quantitative structure-activity relationship (QSAR) analysis. Key strategies, methods for rational design to optimize AMP performance are available. An ideal “designer” molecule of an AMP family exerts strong antimicrobial activity on the target bug(s) without any harmful side effects on the protected organism. However, the clinical application faces challenges: stability, delivery, and toxicity. To address these limitations and enhance AMP stability and therapeutic efficacy, several key strategies have been explored: formulation, self-assembled nanotechnology of AMPs, internal structural (including stereochemical) modification, cyclization, and terminal modification. Functional genomics (emphatically the recently discovered easy-PACId approach) revolutionized rational drug design, providing new ways for antimicrobial drug discovery. Clusters of coregulated genes—often organized as biosynthetic gene complexes (BCGs) or operons—encode enzymes from interacting biosynthetic pathways. These clusters facilitate the discovery of new non-ribosomal peptides (NRPs) and polyketide-like derivatives. This is made possible by their compatibility with modern genetic engineering techniques, such as gene silencing, deletion, or insertion, as well as the replacement of regulatory elements within or surrounding these co-regulated genes. The end-products and intermediates of these biosynthetic pathways are new design peptide candidates. The requirement towards publications appearing in this Research Topic is a significant contribution to the biological and chemical research aiming at to discover new anti-multidrug resistance drug candidate peptides applicable in clinical and veterinary medicine (as well as in plant pathology) to overcome multidrug-resistant bacterial pathogens and epidemics caused by them. Other targets are the eukaryotic parasites, revealing novel modes of action and genetic regulatory mechanisms. by using the methodology of analytical and preparative organic chemistry, classical and molecular biology (microbiology, biochemistry, genetics), and bioinformatics. Each step from the discovery of new molecules leading to the synthesis of a designer peptide of the AMP family, the discovery of novel modes of action, as well as to improving of application potential, may yield new publishable information in our Research Topic.

We welcome Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:
• Natural sources of peptide derivatives targeting new bugs and/or using novel modes of action, lacking hazardous features.
• Results of experiments leading to the discovery and synthesis of a designer peptide, including the target ranges and side effects of the new molecules.
• Genetic regulation of the biosynthesis of non-ribosomal peptides.
• Data related to resistances, cross-resistances, and collateral sensitivities.
• Attempts to “smuggle” cDNA templates into the cells of organisms to be protected, aimed at achieving intracellular biosynthesis of protecting AMP molecules.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• Mini Review
• Opinion
• Original Research
• Perspective
• Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• Mini Review
• Opinion
• Original Research
• Perspective
• Review

Keywords: Antimicrobial Peptide, Single-gene encoded peptide, Designer peptide, Plant immune signaling, Non-ribosomal template peptide, Polyketide-derivative, Genetic regulation, easyPACId, Multidrug resistance, Intracellular biosynthesis from cDNA template

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.