Open research questions in Antimicrobial Peptides and Activities

What the literature leaves open

• Experimental validation of the simulation-derived predictions is needed, - Evaluation of the framework outside the sampled design space is required, - Investigation of lower thresholds for a more favorable multi-objective trade-off is suggested, - Further research on the optimization of treatment amplitude Umax is necessary

  Predictive modeling of probiotic-pathogen interactions under threshold-triggered antimicrobial peptide control · 2026 · DOI

• The study of AMPs in extremophytic plants is challenging due to the limited availability of genomic resources. The identification and characterization of AMP gene families require specialized bioinformatics tools and expertise. The analysis of gene expression under salt-stress conditions can be complex and requires careful experimental design and data analysis.

  Genome-Wide Identification, Evolutionary Characterization, and Salt-Stress Expression Profiling of Antimicrobial Peptide Gene Families in the Xerophytic Recretohalophyte Reaumuria soongarica · 2026 · DOI

• The repertoires of AMPs remain poorly characterized in extremophytic plants. There is a need to define AMP gene families and their expression under stress conditions in these plants. The study of AMPs in Reaumuria soongarica can provide insights into their role in stress adaptation and innate immunity.

  Genome-Wide Identification, Evolutionary Characterization, and Salt-Stress Expression Profiling of Antimicrobial Peptide Gene Families in the Xerophytic Recretohalophyte Reaumuria soongarica · 2026 · DOI

• Rational peptide engineering and smart nanocarrier-based delivery, - Host-directed induction of endogenous LL-37 via vitamin D and short-chain fatty acid pathways, - Standardisation of salivary/gingival crevicular fluid LL-37 as a non-invasive biomarker

  LL-37-based oral antimicrobial therapeutics: translational challenges and future directions—a narrative review · 2026 · DOI

• The clinical application of LL-37 is hindered by proteolytic degradation and cytotoxicity. There is a need for standardization of salivary LL-37 as a biomarker. The development of LL-37 as a therapeutic agent is stalled due to several challenges.

  LL-37-based oral antimicrobial therapeutics: translational challenges and future directions—a narrative review · 2026 · DOI

• The study only tested a limited number of peptides and lysins, - The experiments were conducted in a laboratory setting, - The study did not investigate the potential toxicity of the engineered lysins to eukaryotic cells

  Experimental screening and structure-informed engineering of peptide-fused bacteriophage lysins with enhanced activity against Gram-negative bacteria · 2026 · DOI

• The limited activity of bacteriophage-derived lysins against Gram-negative bacteria under physiological conditions. The need for a more efficient and rational approach to selecting peptides for lysin fusion.

  Experimental screening and structure-informed engineering of peptide-fused bacteriophage lysins with enhanced activity against Gram-negative bacteria · 2026 · DOI

• Limited understanding of the direct response of neutrophils and monocytes to biomaterials and bioactive compounds. Need for effective strategies to modulate excessive inflammation following implant insertion. Gap in knowledge on the impact of purified bioactive extracts on leukocyte activity and implant outcomes.

  Strengthened Anti-Inflammatory Potential of a Purified Antimicrobial Peptide Extract in Leukocyte–Biomaterial Interactions · 2026 · DOI

• developing innovative therapies such as AMP-integrated smart biomaterials and targeted peptide delivery systems, - evaluating the safety, efficacy, and pharmacokinetics of AMPs in treating a range of infections, - exploring the enhanced antibacterial properties of rationally designed variants of bacitracin

  Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense · 2025 · DOI

• The limitations of traditional antibiotic therapy due to rising antimicrobial resistance. The need for new approaches in wound healing, given the high prevalence and costs of chronic wounds. The lack of understanding of the specific roles of antimicrobial peptides in promoting wound healing.

  Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense · 2025 · DOI

• The study only evaluated the attachment of AMPs to hydrogels and their antibacterial efficacy, without considering other potential applications or limitations. The study used a limited number of AMPs and hydrogel types, which may not be representative of all possible combinations. The study did not investigate the long-term stability and durability of the AMP-hydrogel complexes.

  Antibacterial and Hemolytic Activity of Antimicrobial Hydrogels Utilizing Immobilized Antimicrobial Peptides · 2024 · DOI

• Investigating the attachment of AMPs to other types of materials and surfaces. Evaluating the antibacterial efficacy of AMP-hydrogel complexes against a wider range of bacteria. Studying the long-term stability and durability of AMP-hydrogel complexes.

  Antibacterial and Hemolytic Activity of Antimicrobial Hydrogels Utilizing Immobilized Antimicrobial Peptides · 2024 · DOI

• AMP-Designer excels in creating AMPs targeting specific strains despite limited data availability, with a top candidate displaying a minimum inhibitory concentration of 2.

  Discovery of antimicrobial peptides with notable antibacterial potency by an LLM-based foundation model · 2025 · DOI

• Further preclinical development and clinical trials are warranted to explore SK1260 as a viable alternative in the fight against AMR.

  Broad-spectrum antimicrobial activity and in vivo efficacy of SK1260 against bacterial pathogens · 2025 · DOI

• Despite their importance, the mechanisms by which AMPs interact with microbes and the host immune system remain understudied due to the lack of genetic tools.

  Genetic dissection of defensin signaling in skin immunity and psoriasis 2578 · 2025 · DOI

• This paper will also discuss potential areas for further investigation into the anti-cancer effects of Ple and its derivatives, drawing insights from microbiological research.

  From antimicrobial to anticancer: unraveling the potential of pleurocidin and pleurocidin-derived peptides in the treatment of cancers · 2024 · DOI

• While most AMP databases focus on terrestrial eukaryotes, marine cephalopods represent a promising yet underexplored source.

  Unveiling Encrypted Antimicrobial Peptides from Cephalopods’ Salivary Glands: A Proteolysis-Driven Virtual Approach · 2024 · DOI

• However, it remains uncertain which molecules are responsible for inducing hyperpolarization and what the underlying molecular mechanisms are.

  Chemically diverse antimicrobial peptides induce hyperpolarization of the E. coli membrane · 2024 · DOI

• The interplay between antimicrobial peptides and amyloid proteins is crucial for uncovering new insights into immune defense and disease mechanisms, bridging critical gaps in understanding infectious and neurodegenerative diseases.

  Interplay between Antimicrobial Peptides and Amyloid Proteins in Host Defense and Disease Modulation · 2024 · DOI

• However, complex interactions, molecular mechanisms, and physiological applications are not fully understood.

  Interplay between Antimicrobial Peptides and Amyloid Proteins in Host Defense and Disease Modulation · 2024 · DOI

• Further study of the signal peptide of anuran AMPs. Investigation of the role of enhancers and transcription factors in the expression of anuran skin-secreted AMPs. Examination of the evolution of skin-secreted AMPs in other anuran species.

  The Rana sylvatica skin-secreted antimicrobial peptide (AMP) gene repertoire highlights broader patterns in anuran AMP evolution · 2026 · DOI

• Our 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 · DOI

• The lack of understanding of the isolation, purification, and characterization methodologies of AMPs from Bombyx mori. The need for the development of peptide engineering, recombinant expression systems, and nano formulation techniques to improve the therapeutic potential of AMPs derived from silkworms.

  ANTIMICROBIAL PEPTIDES FROM Bombyx mori: PHARMACEUTICAL CONTRIBUTIONS, APPLICATIONS, AND RECENT DISCOVERIES · 2026 · DOI

• Research on plant elicitor peptides in citrus has remained largely unexplored. The regulatory role of CsPep in citrus canker resistance and plant regeneration was unknown.

  Identification of plant elicitor peptides in citrus and the dual regulatory effects of CsPep on plant regeneration and canker resistance · 2026 · DOI

• Future research should explore the conservation of this mechanism across diverse citrus species and evaluate its field efficacy, further validating its potential for sustain- able citrus production. Furthermore, whether CsPep-medi- ated resistance involves stomatal immunity remains to be determined. It remains to be seen whether a similar stomatal defense mechanism is engaged in citrus in response to CsPep treatment, and whether this regulation involves homologous ion channels, which represent important areas for future investigation.

  Identification of plant elicitor peptides in citrus and the dual regulatory effects of CsPep on plant regeneration and canker resistance · 2026 · DOI

Most-cited papers in Antimicrobial Peptides and Activities

• Antimicrobial peptides of multicellular organisms · Nature · 2002 · 7,274 citations
• Enantiomer-dependent immunological response to chiral nanoparticles · Nature · 2022 · 617 citations
• Discovery of antimicrobial peptides in the global microbiome with machine learning · Cell · 2024 · 339 citations
• Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii · Nature Chemical Biology · 2023 · 324 citations
• Design of target specific peptide inhibitors using generative deep learning and molecular dynamics simulations · Nature Communications · 2024 · 295 citations
• Identification of potent antimicrobial peptides via a machine-learning pipeline that mines the entire space of peptide sequences · Nature Biomedical Engineering · 2023 · 265 citations
• Bacterial cell‐wall recycling · Annals of the New York Academy of Sciences · 2012 · 262 citations
• Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice · Burns & Trauma · 2022 · 260 citations
• Antimicrobial Peptides · Drugs · 2003 · 251 citations
• Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug‐resistant infections · Medicinal Research Reviews · 2022 · 230 citations

Most recent work

• AllTheBacteria: a community resource empowers biology and discovers novel peptide antibiotics · bioRxiv · 2026
• Antimicrobial peptides: natural templates for next-generation therapeutics against antimicrobial resistance · Frontiers in Cellular and Infection Microbiology · 2026
• Injectable Peptide Therapy: A Primer for Orthopaedic and Sports Medicine Physicians · The American Journal of Sports Medicine · 2026
• Overcoming multidrug resistance: antimicrobial peptides as a next-generation therapeutic strategy · Frontiers in Cellular and Infection Microbiology · 2026
• Self-assembled nanonetworks of highly stable gemini surfactant-like peptides: antibacterial mechanisms, self-assembly characteristics, and in vivo anti-infection potential · Journal of Nanobiotechnology · 2026
• Scaling SMILES-Based Chemical Language Models for Therapeutic Peptide Engineering · bioRxiv · 2026
• Time-resolved phenotyping at subcellular resolution reveals shared principles and key trade-offs across antimicrobial peptide activities · bioRxiv · 2026
• Bacterial cell fate under stress: lipid remodeling and antimicrobial peptide attack · npj Antimicrobials and Resistance · 2026
• Antimicrobial Peptide Spampcin 56–86 Controls Fusarium graminearum and Mycotoxin via Membrane Disruption and Oxidative Burst with TRI Repression: A Strategy for Wheat Protection · Journal of Agricultural and Food Chemistry · 2026
• Identification of two novel peptides with antibiofilm and antimicrobial effects from ovotransferrin hydrolysates using peptidomic and regression-based machine learning approach · LWT · 2026

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