Open research questions in Antimicrobial Peptides and Activities
498 gap statements mined from Antimicrobial Peptides and Activities papers in our 7.9M-paper local library, which holds 1,964 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The lack of understanding of the mechanistic insights of β-defensin 130 on ETEC-K88 infection. The need to investigate the interaction relationship between gut microbiota and metabolites. The limited knowledge on the effect of β-defensin 130 on intestinal metabolic pathways.
β-defensin 130 Counteracts ETEC-K88 Infection in Mice: Mechanistic Insights from Gut Microbiome and LC-MS-Based Metabolomic Correlation Analysis · 2026 · DOIThe paper highlights the need to eliminate the inherent disadvantages of antimicrobial peptides, including insufficient activity.
Antimicrobial Peptides, Their Production, and Potential in the Fight Against Antibiotic-Resistant Pathogens · 2025 · DOIThe paper identifies the need for novel antimicrobial agents to address the resistance crisis. There is a gap in the development of efficient methods for discovering and testing antimicrobial peptides. The study highlights the importance of understanding the mechanisms of action of antimicrobial peptides.
Machine Learning-Based Discovery of Antimicrobial Peptides and Their Antibacterial Activity Against Staphylococcus aureus · 2025 · DOIThe need for detailed mechanism studies of marine peptides. The need for large-scale production and clinical evaluations of marine peptides. The need to investigate the potential synergistic effects of marine peptide combinations with existing medicines.
The need for new antimicrobials to combat Gram-positive pathogens. The lack of understanding of the properties and activities of circular bacteriocins. The need to develop new methods for the purification and characterization of circular bacteriocins.
Characterization of Flexusin A, a Novel Circular Bacteriocin Produced by Marine Bacterium Bacillus flexus R29-2 · 2025 · DOIThe development of new antimicrobial agents that can effectively combat resistant bacterial strains. The need to overcome the limitations of existing antimicrobial agents, such as stability and toxicity issues. The challenge of scaling up the production of the novel antimicrobial peptide for clinical use.
Novel Anti-MRSA Peptide from Mangrove-Derived Virgibacillus chiguensis FN33 Supported by Genomics and Molecular Dynamics · 2025 · DOIThe need for new antimicrobial agents to combat antibiotic-resistant bacteria. The challenges associated with the development of antimicrobial peptides, such as stability and toxicity. The lack of effective solutions to the growing problem of antibiotic resistance.
The complexity of the model should ideally align with the size of the dataset, ensuring a proportional relationship between model complexity and dataset scale. Overfitting resulting from excessive model complexity. The need to select an optimal k-value to balance model complexity and generalization ability.
Comprehensive summaries of AMPs' roles in skin cancer and related current clinical developments remain scarce, despite abundant emerging evidence of pro- and anti-tumour properties in other fields.
Catestatin (CST), a neuroendocrine antimicrobial peptide produced by neurons and epithelial cells, has been implicated in skin defense against pathogens such as MRSA, though its mechanisms remain unclear.
The neuroendocrine peptide catestatin promotes clearance of cutaneous Staphylococcus aureus through mast cell Mrgpr activation · 2026 · DOIHowever, the broader physiological significance of the HD5-P2Y11 interaction remains poorly understood.
Human enteric defensin 5 protects intestinal barrier integrity via cell state–dependent P2Y11–FAK–Rac1 signaling · 2026 · DOIHowever, obtaining these peptides solely through traditional wet laboratory experiments is costly and time-consuming, and peptides identified by current computer-assisted predictive models largely lack validation of their effects via wet laboratory experiments.
Machine learning accelerates the discovery of epitope-based dual-bioactive peptides against skin infections · 2024 · DOIHowever, the potential AMPs and AMP resistance genes (AMPRGs) of gut microbes in different age groups have not been thoroughly assessed.
Antimicrobial Peptides From the Gut Microbiome of the Centenarians: Diversification of Biosynthesis and Youthful Development of Resistance Genes · 2024 · DOIOur findings describe a family of anuran skin-secreted AMP genes that has grown and diversified in a manner similar to other AMP families, but many of the factors shaping the evolution and expression of these AMP genes remain unclear. While this is compelling, the underlying exon shuffling process has yet to be demonstrated in anuran AMP genes, and it remains unclear why the signal peptide sequence is so constrained.
The Rana sylvatica skin-secreted antimicrobial peptide (AMP) gene repertoire highlights broader patterns in anuran AMP evolution · 2026 · DOIThe paper analyzes membrane integrity data only within the 30–60 minute window post-peptide treatment; the fate of bacterial cells and extent of lipid remodeling at longer timepoints (beyond 2 hours) or after complete membrane disruption is not characterized, particularly whether surviving cells with altered lipid composition exhibit stress-induced tolerance mechanisms.
This study did not include a Defb25 knockout model - The study was not able to entirely define the precise fibroblast subsets expressing Defb25 - Sparse defensin transcript detection limited robust fibroblast…
A stromal β-defensin, DEFB124, contributes to cutaneous host defense against Staphylococcus aureus. · 2026 · DOIFuture genetic studies will be important to further define the physiological and cell-type-specific contributions of Defb25 to skin immunity - scRNA-seq analyses could be used to further define the precise fibroblast subsets expressing…
A stromal β-defensin, DEFB124, contributes to cutaneous host defense against Staphylococcus aureus. · 2026 · DOIClarifying the selectivity mechanisms exhibited by AMPs when interacting with the membranes of the target organism - Exploring new technologies, including artificial intelligence, to improve AMPs - Investigating unexplored marine microorganisms as a promising reservoir of new bioactive…
Antimicrobial Peptides, Their Production, and Potential in the Fight Against Antibiotic-Resistant Pathogens · 2025 · DOIInvestigating the peptides' activity against Gram-negative strains, - Analyzing the potential toxicity of the peptides to human cells, - Developing the peptides as anti-drug-resistant…
Machine Learning-Based Discovery of Antimicrobial Peptides and Their Antibacterial Activity Against Staphylococcus aureus · 2025 · DOIInstability and limited scalability, - Rapid proteolytic degradation, - Poor metabolic stability and limited intestinal epithelial permeability, - Short in vivo…
Marine Antimicrobial Peptides: Advances in Discovery, Multifunctional Mechanisms, and Therapeutic Translation Challenges · 2025 · DOIRational AMPs design to enhance efficacy and safety, - Synergistic combination strategies, - De novo peptide design using artificial intelligence and machine…
Marine Antimicrobial Peptides: Advances in Discovery, Multifunctional Mechanisms, and Therapeutic Translation Challenges · 2025 · DOIThe development of multidrug-resistant pathogens and the growing incidence of cancer pose significant challenges to global health. The limitations!!!!!
The Invertebrate-Derived Antimicrobial Peptide Cm-p5 Induces Cell Death and ROS Production in Melanoma Cells · 2025 · DOIThe study did not investigate the long-term effects of the antimicrobial peptides, - The sample size of the macrogenomic sources was limited, - The study only evaluated the cytotoxicity of the three peptides using HEK293T…
Synthesis and Evaluation of Aquatic Antimicrobial Peptides Derived from Marine Metagenomes Using a High-Throughput Screening Approach · 2025 · DOIInformation on the characteristics of bacteriocin-producing Virgibacillus is quite limited, - The study did not investigate the in vivo efficacy of FN33 AMP, - The stability of FN33 AMP was only evaluated under certain…
Novel Anti-MRSA Peptide from Mangrove-Derived Virgibacillus chiguensis FN33 Supported by Genomics and Molecular Dynamics · 2025 · DOIInvestigating the use of larger ESM2 variants, - Exploring the application of the proposed models to other domains, - Further analysis of the impact of classifier performance on AMP design…
Most-cited papers in Antimicrobial Peptides and Activities
- Antimicrobial peptides of multicellular organisms · Nature · 2002 · 7,274 citations
- DBAASP v3: database of antimicrobial/cytotoxic activity and structure of peptides as a resource for development of new therapeutics · Nucleic Acids Research · 2020 · 773 citations
- Antimicrobial peptides: mechanism of action, activity and clinical potential · Military Medical Research · 2021 · 638 citations
- Enantiomer-dependent immunological response to chiral nanoparticles · Nature · 2022 · 617 citations
- Mechanism of Antimicrobial Peptides: Antimicrobial, Anti-Inflammatory and Antibiofilm Activities · International Journal of Molecular Sciences · 2021 · 544 citations
- Antibacterial fatty acids: An update of possible mechanisms of action and implications in the development of the next-generation of antibacterial agents · Progress in Lipid Research · 2021 · 496 citations
- A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens · Nature Microbiology · 2020 · 480 citations
- Antimicrobial Peptides: A New Hope in Biomedical and Pharmaceutical Fields · Frontiers in Cellular and Infection Microbiology · 2021 · 469 citations
- Antimicrobial peptides (AMPs): A promising class of antimicrobial compounds · Journal of Applied Microbiology · 2021 · 442 citations
- Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides · Scientific Reports · 2020 · 436 citations
Most recent work
- AllTheBacteria: a community resource empowers biology and discovers novel peptide antibiotics · bioRxiv · 2026
- Artificial Intelligence as a Catalyst for Antimicrobial Discovery: From Predictive Models to De Novo Design · Microorganisms · 2026
- Antimicrobial peptides: natural templates for next-generation therapeutics against antimicrobial resistance · Frontiers in Cellular and Infection Microbiology · 2026
- Artificial Intelligence and the Discovery of Antibiotics: Reinventing with Opportunities, Challenges, and Clinical Translation · Antibiotics · 2026
- Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians · The American Journal of Sports Medicine · 2026
- Fatty Acid-Conjugated Antimicrobial Peptides: Advances in Design, Activity, and Therapeutic Potential · Journal of Medicinal Chemistry · 2026
- Current Status of Molecular Dynamics Simulations of Membrane Permeabilization by Antimicrobial Peptides and Pore-Forming Proteins: A Review · Journal of Chemical Information and Modeling · 2026
- D-amino acid substitution and cyclization enhance the stability and antimicrobial activity of arginine-rich peptides · Microbiology · 2026
- Antimicrobial Peptides as Novel Ecological Approaches to Caries Prevention · Drug Design Development and Therapy · 2026
- Harnessing AI for Antimicrobial Peptide Innovation against Multidrug Resistance · JACS Au · 2026
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