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| Main Authors: | , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
ACS infectious diseases
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/41363146/ |
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Table of Contents:
- Marine-Inspired Antimicrobial Peptides Disrupt Gene Expression at the DNA Level. Beyer, Luisa I Thoma, Johannes Acha Alarcon, Leonarda Unksov, Ivan N Karlsson, Roger Inda-Díaz, Juan S Tietze, Alesia A Antimicrobial Peptides Gene Expression Regulation, Bacterial Streptomyces Microbial Sensitivity Tests Anti-Bacterial Agents Proteomics Uropathogenic Escherichia coli DNA, Bacterial Proteome Genome mining of sp. H-KF8 combined with sequence engineering yielded two serum-stable, noncytotoxic, nonlytic antimicrobial peptides, L3 and L3-K. Initial studies in uropathogenic suggested membrane effects and nucleoid relaxation, prompting a comprehensive investigation of their mode of action. In this study tandem mass tag (TMT)-based quantitative proteomics revealed extensive proteome remodeling, with 175 and 120 differentially expressed proteins (DEPs) after treatment with L3 and L3-K, respectively. L3 induced predominantly upregulated responses linked to metabolism, RNA processing, transport, and homeostasis, whereas L3-K mainly caused the downregulation of proteins involved in metabolism, transport, and cell structure. Both peptides disrupted ABC transporter-mediated nutrient uptake and elicited stress responses, while L3 specifically perturbed the regulon, indicative of broader transcriptional dysregulation. Complementary fluorescent dye displacement and in vitro transcription/translation assays demonstrated nonspecific DNA binding, stronger for L3 than L3-K, and potent inhibition of transcriptional and translational processes. Strikingly, inhibitory concentrations paralleled their minimum inhibitory concentrations, directly linking DNA binding and interference with central information processing to antimicrobial activity. These findings reveal that L3 and L3-K primarily act by targeting DNA and interfering with the transcription-translation machinery. Beyond offering mechanistic insights, this study underscores peptides' potential to act as scaffolds for next-generation antimicrobial peptides with DNA-binding and nonmembrane-lytic activity.