Overview
LL-37 is a naturally occurring antimicrobial peptide found in humans, belonging to a family of host defense molecules known as cathelicidins. It is produced by various cell types, including neutrophils, macrophages, and epithelial cells, and is considered one of the only known human cathelicidin peptides. LL-37 has drawn significant scientific interest due to its ability to interact with nucleic acids, bacterial membranes, and components of the immune system, making it a subject of broad inquiry in microbiology and immunology research. Also referred to by names such as CAP-18 and ropocamptide, this peptide has been studied in contexts ranging from bacterial resistance to wound-healing models, including research involving chronic diabetic wound environments. Like all peptides on this reference site, LL-37 is intended strictly for laboratory research purposes and is not approved for human use or consumption.
Research & Bioactivity
LL-37 is a human cathelicidin host defense peptide that has attracted significant research interest due to its wide expression across cell types including neutrophils, macrophages, and epithelial cells. Researchers have studied its interactions with nucleic acids, with findings suggesting that LL-37 forms complexes with DNA that may influence the structure of neutrophil extracellular traps, a subject examined using techniques such as phage lambda DNA modeling in laboratory settings. Studies have also investigated LL-37's antimicrobial properties in the context of drug-resistant bacterial pathogens, including Pseudomonas aeruginosa and Shiga toxin-producing Escherichia coli, with in vitro research exploring how the peptide contributes to bacterial membrane disruption and biofilm inhibition. Research has examined LL-37 expression in mesenchymal stem cell models, with findings indicating that three-dimensional culture environments may influence the peptide's antimicrobial activity against clinically relevant organisms. Additionally, preclinical studies have incorporated LL-37 into experimental biomaterial systems, such as hydrogel microneedle constructs, to investigate its potential role in antibacterial and tissue-related biological processes in animal models of chronic wound conditions.
Published Research
Human cathelicidin peptide LL-37 compacts nucleic acids and alters neutrophil extracellular trap structure.
Zielke C, Rad B, Nielsen JE, Li J, Pimcharoen S, et al. — 2026
The human cathelicidin host defense peptide LL-37 is expressed by many cell types, including neutrophils, macrophages, and epithelial cells, and forms complexes with nucleic acids that can have either beneficial or detrimental health effects. We suggest that these differential impacts are directly connected to the extent of nucleic acid binding by LL-37. Here, we use phage λ DNA and techniques such as high-resolution video microscopy, gel electrophoresis, circular dichroism, and displacement assays to show that LL-37 binds non-specifically to dsDNA, condensing it, followed by formation of progressively larger complexes from smaller domains, until "complete" complexation is attained at a (w/w) ratio of DNA/LL-37 of 1:1.7. The morphology of these complexes is concentration-dependent, with relatively low LL-37 amounts yielding loosely aggregated DNA structures and higher LL-37 concentrations leading to well-defined, disc-like complexes of about 150 nm in diameter. The condensation of nucleic acids, which causes a loss of the characteristic B-DNA features, results from interactions of the phosphodiester backbone with cationic amino acid side chains of the peptide at physiological pH, most likely in A-T rich sequences of the nucleic acid. Our results show that the α-helical structure of the peptide with its amphipathic and hydrophobic surfaces is essential. Finally, we show that LL-37 complexation alters the structure of neutrophil extracellular traps (NETs), causing a significant reduction in projected NET area at high LL-37 concentrations. Our data suggest that LL-37 helps prevent nucleic acid dispersal and condenses dsDNA, which may impact the biophysics of NET clearance.
Responsive dual-layer hydrogel microneedles accelerate diabetic wound healing via antibacterial and enzyme cascade regulation.
Zhang Y, Di T, Wu Q, Deng K, Fu X, et al. — 2026
Chronic diabetic wounds do not heal and are often accompanied by infections and poor angiogenesis. We have made a two-layered PVA/CS composite hydrogel MN-CL patch, which has antibacterial, immunoregulatory, and pro-healing properties. The needle tips were loaded with the antimicrobial peptide LL-37 to achieve immediate bactericidal action when the needle penetrates the bacterial membrane, and the hydrogel base contained a GOx/CAT cascade system that could respond to hyperglycemic and acidic microenvironments. This system regulates the local glucose and ROS levels, promoting the transition of the wound from the inflammatory phase to the proliferative phase. In vitro experiments showed that the MN-CL patch had a strong antibacterial effect on bacteria, it could promote macrophages to change from M1 type to M2 type, and it could also promote the proliferation, migration, and angiogenesis of endothelial cells. Transcriptome analysis showed that the effects were mainly caused by the inhibition of inflammatory pathways such as IL-1 and NF-κB signaling and the activation of tissue repair-related pathways. In a diabetic rat infection model, the MN-CL patch greatly improved the rate of wound healing, angiogenesis, and collagen accumulation, indicating that this method may have potential for clinical application in treating chronic wounds.
Characterization of two exoU/exoS carbapenem-non-susceptible Pseudomonas aeruginosa co-colonizing the lung of a bacterial pneumonia patient.
Yan Y, Qian L, Feng X, Zhang F, Tang M, et al. — 2026
BACKGROUND: Pseudomonas aeruginosa is a major cause of acute nosocomial infections, as well as chronic respiratory infections associated with cystic fibrosis (CF). In chronic lung infections, P. aeruginosa populations typically exhibit extensive phenotypic variation, a trait linked to their need to undergo pathoadaptive mutations to counteract host-derived selective pressures. METHODS: In this study, two clonally related P. aeruginosa isolates, SCPA07 and SCPA08, were identified to coexist in a single bronchoalveolar lavage fluid (BALF) sample from a patient with bacterial pneumonia. Whole-genome sequencing (WGS) was conducted to characterize their genetic background, as well as antimicrobial resistance and virulence gene profiles. A comprehensive analysis of phylogenetic relationships and comparative genomic features of the two isolates was conducted using a panel of bioinformatics tools. Their antimicrobial resistance mechanisms were elucidated via gene sequence analysis and quantitative reverse-transcription PCR (qRT-PCR). A series of phenotypic experiments, including growth, biofilm formation, environmental stress, and virulence assays, and others were performed to characterize their phenotypic traits. RESULTS: Antimicrobial susceptibility assay showed that both strains were carbapenem-non-susceptible (defined as intermediate or resistant according to the Clinical and Laboratory Standards Institute (CLSI) guidelines). Genomic analysis revealed that they are 'hypermutator' strains and harbor both the exoS and exoU virulence genes, indicating an increased propensity for persistent host infection and high virulence potential. Both strains harbored mutations in oprD, and exhibited elevated expression of AmpC β-lactamase and the efflux pump MexB, which most likely contributed to their non-susceptibility to carbapenems. Despite harboring nucleotide variations at only ten genetic loci, these two strains exhibited distinct phenotypic traits: SCPA07 showed rapid growth, strong biofilm formation, high virulence, and growth advantages under iron limitation and serum stress; in contrast, its variant SCPA08 had slow growth, poor motility, reduced pyocyanin production, low virulence, and increased tolerance to the host antimicrobials human cathelicidin LL-37 and hydrogen peroxide (HO). These phenotypic variations are proposed to be primarily driven by genetic mutations affecting the O-antigen biosynthesis, iron utilization, Porin D, and other determinants. CONCLUSIONS: This study elucidates the divergent adaptive evolutionary strategies of a single exoS/exoU P. aeruginosa clone within the host during bacterial pneumonia, as well as their critical role in shaping the bacterium's virulence and adaptability, which sheds light on the within-host evolution dynamics of P. aeruginosa populations during their pathogenesis and persistence in the lung.
Cellulose-based hydrogel matrix enhances antimicrobial and biofilm-inhibitory responses of palatal mesenchymal stem cells.
Bicer M, Sener F, Öztürk E, Fidan Ö — 2026
Mesenchymal stem cells (MSCs) have emerged as promising alternatives to fight drug-resistant bacterial infections. This study investigates the antibacterial activity of palatal adipose tissue-derived MSCs (PMSCs), particularly when cultured within a 3D nanofibrillar cellulose hydrogel, against four clinically relevant pathogens: K6, ATCC 25,923, K9 and O157:H7. This study showed that both PMSCs alone and PMSCs in 3D cellulose-based hydrogel effectively inhibited the growth of bacterial burden. Notably, PMSCs cultured in the 3D system demonstrated an excellent effect, reducing bacterial burden by up to 14 log in and 12 log in K6 at a 120 µL inoculum after 2 h of incubation. RT-PCR and immunocytochemical analyses found out a remarkable upregulation of the Cathelicidin (LL-37) in PMSCs 3D cultures compared to PMSCs. Furthermore, 3D cellulose-based hydrogel exhibited a significant biofilm-inhibitory effect, reaching a 57.65% reduction. The results demonstrated the importance of 3D cellulose-based hydrogel for treating antibiotic-resistant infections. PMSC therapy based on 3D hydrogel may therefore be offered as more effective antimicrobial agent to overcome drug-resistant bacterial infections.
Three-Dimensional Culture Enhances the Antimicrobial Activity of Mesenchymal Stem Cells Against Shiga Toxin-Producing Escherichia coli O157:H7 In Vitro.
Bicer M, Öztürk E, Sener F, Türkyılmaz S, Fidan Ö — 2026
AIMS: This study examines the in vitro antibacterial activity of palatal adipose tissue-derived mesenchymal stem cells (PAT-MSCs) and the expression of antimicrobial peptide LL-37, with a particular focus on the effect of three-dimensional (3D) nanofibrillar cellulose-based hydrogel, against Shiga toxin producing Escherichia coli (STEC) harboring stx1 and/or stx2 genes isolated from mastitis milk in Turkey. METHODS AND RESULTS: The antibacterial activity of conventionally cultured PAT-MSCs and 3D-cultured PAT-MSCs (PAT-MSCs-3D) was evaluated against STEC isolates and Escherichia coli ATCC 35150 using quantitative colony-forming unit (CFU) assay. The expression levels of antimicrobial peptide (AMP)-encoding genes were evaluated by quantitative real-time PCR, and AMP production was further validated by immunocytochemical staining. The results indicated that PAT-MSCs-3D exhibited significantly enhanced antibacterial efficacy, resulting in marked bacterial inhibition of all tested STEC strains, with bacterial reductions reaching up to 6-7 log under specific experimental conditions. Molecular and immunocytochemical analyses demonstrated increased expression of the antimicrobial peptide LL-37 in PAT-MSCs-3D compared to 2D cultures. CONCLUSIONS: Our results show that culturing PAT-MSCs in 3D conditions leads to a significant enhancement in their antimicrobial properties, which could be linked to the upregulation of LL-37.