Locilex (pexiganan acetate) / PLx Pharma - LARVOL DELTA

Adaptive Response of Escherichia coli to Pexiganan: Insights from Genomic Analysis. (PubMed, Antibiotics (Basel)) - "In addition, the missense mutation was detected in the membrane biosynthesis genes pssA and clsB. In vivo infection models, targeted functional genomics, and comprehensive phenotypic cross-resistance testing will be required to validate our results."

Journal • Infectious Disease

Tryptophan substitutions reveal cooperative membrane transitions and aromatic interactions associated with membrane permeabilisation in CM15 and MSI-78 peptide analogues. (PubMed, Bioorg Chem) - "These simulations also showed sequence-dependent differences in peptide insertion and helical stability, providing a structural framework to interpret the experimentally observed differences in membrane permeabilisation trends. Oxidation product patterns of peptides in LUVs induced by water-soluble oxygenated free radicals favoured monomer di-tyrosine dimerisation, supporting the formation of peptide assemblies associated to the membrane and localized lipidic defects that may enhance calcein release and contribute with the observed antimicrobial activity."

Journal

ROS/pH dual-responsive tannic acid-coated nanoparticle-integrated hyaluronic acid hydrogel for antibacterial and pro-healing effects on diabetic wounds in vitro. (PubMed, RSC Adv) - "Mesoporous silica nanoparticles (MSNs) were co-loaded with the antimicrobial peptide Pexiganan (AMP, EE% = 90.10%) and Zn2+ (EE% = 33.71%), then coated with a tannic acid-Zn2+ metal-phenolic network (TA-Zn2+ MPN) to form TAZNP nanoparticles, which were subsequently embedded in a dynamically crosslinked ADH-HA/OHA hydrazone hydrogel matrix...Flow cytometry confirmed genuine M1-to-M2 phenotypic switching, with the M1 proportion reduced from 60.61% to 25.92% and the M2 proportion increased from 35.11% to 75.44%. These results demonstrate that TAZNP/ADH-OHA Gel integrates microenvironment-responsive synchronized co-delivery with antibacterial, antioxidant, pro-angiogenic, and immunomodulatory activities, providing a promising multifunctional platform for diabetic wound management."

Journal • Preclinical • Diabetes • Infectious Disease • IL10 • TNFA

Unveiling the Potential of Magainin Derivatives against Candida Species. (PubMed, J Med Chem) - "These findings indicate a concentration-dependent mixed mode of action combining metabolic stress at lower exposure and membrane disruption at higher concentrations. MSI-78 (4-20) therefore represents a magainin-derived scaffold for antifungal development."

Journal

Pharmacokinetics determine persister formation in Escherichia coli. (PubMed, JAC Antimicrob Resist) - "Escherichia coli cells that were either primed or not with the antimicrobial peptide pexiganan were subjected to different pharmacokinetics of pexiganan using a set-up with small chemostats...This finding provides proof of principle that pharmacokinetics, which can be influenced by treatment procedures, has consequences for persister formation. Our results suggest that faster pharmacokinetics could minimize persister numbers and hence lower the risks of bacterial infection relapse and resistance evolution."

Journal • PK/PD data • Infectious Disease

The discovery of novel antimicrobial peptides against multidrug-resistant bacteria based on thioether cyclization and unnatural amino acid incorporation strategies. (PubMed, Bioorg Chem) - "Previously, we designed a hybrid peptide 13D, by fusing fragments of sC184b (1-9) and MSI-78 (10-13)...Importantly, P10 achieved significant therapeutic efficacy in a murine model of acute peritonitis induced by MDR P. aeruginosa. These findings suggest that P10 is a promising therapeutic candidate against MDR bacterial infections."

Journal • Infectious Disease

Artificial Intelligence-Driven Discovery and Optimization of Antimicrobial Peptides Targeting ESKAPE Pathogens and Multidrug-Resistant Fungi. (PubMed, Microorganisms) - "Clinically used peptide-derived antibiotics such as polymyxins and daptomycin demonstrate the therapeutic feasibility of peptide-based antimicrobials, while investigational peptides, including pexiganan, illustrate ongoing translational progress. Although no fully AI-designed AMP has yet achieved regulatory approval, the accelerating convergence of computational modeling and experimental validation suggests a rapidly evolving translational landscape. Advancing scalable, surveillance-informed AI frameworks that integrate resistance data, predictive safety modeling and delivery optimization will be essential to accelerate the clinical translation of next-generation, multi-objective AMPs against high-risk resistant pathogens."

Journal • Review

Comparison of agar-based and checkerboard methods to assess phage-antimicrobial synergy in Pseudomonas aeruginosa. (PubMed, J Microbiol Methods) - "In this study, two lytic bacteriophages (BAUNPA1, BAUNPA3) were isolated from wastewater in Türkiye, and the combined efficacy of these phages with antibiotics (ciprofloxacin, colistin, meropenem, tobramycin) or antimicrobial peptides (murepavadin, pexiganan) was evaluated in vitro.Phages were characterized morphologically by electron microscopy and genotypically by restriction fragment length polymorphism, and their different identities were confirmed. Agar-based methods have shown variable results, as plaque morphology does not always correlate quantitatively synergy. This study provides a comparative in vitro framework for assessing phage-antimicrobial interactions and, for the first time, reports reproducible synergy between intact lytic phages and murepavadin or pexiganan, highlighting the importance of methodological approach and application timing in synergy assessments."

Journal

Exploring immobilization strategies of antimicrobial peptides onto MAO-treated titanium to fight MRSA colonization and preserve osteogenic activity. (PubMed, Mater Today Bio) - "The peptide MSI-78 was immobilized either by physical adsorption or covalent grafting, using 1,1'-carbonyldiimidazole (CDI) coupling agent or poly(ethylene glycol) (PEG) spacer...Regardless of the immobilization strategy, bacterial killing appeared to occur via contact-mediated membrane disruption. Moreover, these PEGylated MAO surfaces with adsorbed AMP maintained excellent cytocompatibility with bone-like cells and supported osteogenic response, underscoring their potential as bioactive coatings for titanium implants."

Journal • Infectious Disease

Natural and Synthetic Peptides as Alternatives to Antibiotics in Intestinal Infections-A Review. (PubMed, Antibiotics (Basel)) - "AMPs constitute a promising category endowed with anti-infective activity, especially for therapy of intestinal diseases, which is attributed to their distinctive anti-infective mechanisms, immune-modulating characteristics, and a relatively low propensity for resistance development compared to conventional antibiotics. However, more clinical trials and improvements to their formulation are needed to translate promising in vitro results into reliable patient outcomes."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Inflammation • Pneumonia

Vm-MSI: a Vancomycin-Antimicrobial Peptide Conjugate Combating Resistant Bacteria and Broadening the Antimicrobial Spectrum. (PubMed, Adv Sci (Weinh)) - "Among the acquired conjugates, Vm-MSI showed a 20.18 fold improvement in antimicrobial activity over vancomycin and a 1.95 fold increase compared to the parent peptide MSI-78. In vivo, Vm-MSI displayed remarkable therapeutic efficacy in mouse models of VRSA-induced skin infection and multidrug-resistant A. baumannii-induced lung infection. These findings underscore the great potential of Vm-MSI as an effective treatment for infections caused by vancomycin-resistant and Gram-negative bacteria."

Journal • Dermatology • Infectious Disease • Respiratory Diseases

Peptide-based antibiotics: structure-driven strategies to tackle toxicity and resistance of antimicrobial peptides. (PubMed, Bioorg Med Chem) - "This review focuses on five representative AMPs: daptomycin, pexiganan (MSI-78), murepavadin (POL7080), iseganan (IB-367), and omiganan (MBI-226), and involves an analysis of their clinical development, mechanisms of resistance, toxicity profiles, and resultant outcomes. Furthermore, we discuss prospective peptide design strategies that may effectively address these challenges. Notably, we underscore the potential of structure-based strategies, including amino acid substitutions and conjugation with diverse molecular entities (such as small functional groups, synthetic polymers, peptides, and antibiotics), as promising pathways to mitigate these barriers and advance the development of clinically viable AMP therapeutics."

Journal • Review

AI-guided discovery and optimization of antimicrobial peptides through species-aware language model. (PubMed, Brief Bioinform) - "Notably, peptides 13-5 and 16 demonstrated antimicrobial potency and selectivity comparable to the clinically investigated AMP pexiganan. Our work demonstrates the potential of AI to expedite the discovery of peptide-based antibiotics to combat antibiotic resistance."

Journal

Neutron reflectometry reveals conformational changes in a mechanosensitive protein induced by an antimicrobial peptide in tethered lipid bilayers. (PubMed, J Colloid Interface Sci) - "Addition of 1.6 and 3.2 μM pexiganan resulted in a decrease in the protrusion of MscL (from ∼46 to ∼38 Å). To our knowledge, these findings represent the first direct experimental evidence of a structural change in the C-terminus containing protrusion of MscL, triggered by an antimicrobial peptide."

Journal

Uncovering the genetic basis of Staphylococcus aureus resistance to single antimicrobial peptides and their combinations. (PubMed, iScience) - "Here, we investigated the genetic mechanisms of resistance evolution in Staphylococcus aureus against single and combined AMPs (temporin, melittin, and pexiganan)...The findings suggest that AMP combinations might limit mutation accumulation, while constraining the development of general AMP resistance. The genetic mechanism of resistance is complex, thus careful selection is required for designing effective AMP-based therapies."

Journal

Generation of VacA-targeting guide peptides to increase specific antimicrobial peptide toxicity against Helicobacter pylori. (PubMed, J Biotechnol) - "Guide peptide biopanning provides an effective, scalable method to increase specific activity of antimicrobial peptides based on attraction to a key virulence factor."

Journal • Gastric Cancer • Infectious Disease • Oncology • Solid Tumor

Charge, Hydrophobicity, and Lipid Type Drive Antimicrobial Peptides' Unique Perturbation Ensembles. (PubMed, Biochemistry) - "The membrane curvature changes induced by pexiganan relative to magainin suggest that AMPs with larger charges have more potential in modulating bilayer bending. These insights advance our understanding of AMP-membrane interactions at the molecular level, offering guidance for the design of targeted antimicrobial therapies."

Journal

The discovery of novel antimicrobial peptides against drug-resistant bacteria based on fragments fusion strategy. (PubMed, Eur J Med Chem) - "This study designed a series of antimicrobial peptides by fusing two fragments of antimicrobial peptides sC184b (1-9) and MSI-78 (10-16)...Moreover, 13DKallDab displayed low cytotoxicity and hemolysis in vitro, and significant therapeutic efficacy in a mouse acute peritonitis model. These findings demonstrate that 13DKallDab is a promising antimicrobial agent in counteracting multidrug-resistant bacterial infections."

Journal • Hematological Disorders • Infectious Disease

Evolutionary trajectory of bacterial resistance to antibiotics and antimicrobial peptides in Escherichia coli. (PubMed, mSystems) - "We reveal that E. coli develops resistance to antibiotics, particularly ciprofloxacin and kanamycin, at a notably faster rate than to AMPs...Notably, we demonstrate that trimethoprim-resistant E. coli, with mutations in thyA gene, displays enhanced susceptibility to pexiganan, as evidenced by both in vitro and in vivo studies...Additionally, these antibiotic-resistant strains incur significant fitness costs, particularly in bacterial growth and motility. Most importantly, we find that some antibiotic-resistant strains show collateral sensitivity to specific AMPs in both in vitro and animal infection models, which is conducive to accelerating the development of AMP-based antibacterial treatment."

Journal • Infectious Disease

Assessment of Linear and Cyclic Peptides' Immobilization onto Cross-Linked, Poly(vinyl alcohol)/Cellulose Nanocrystal Nanofibers Electrospun over Quartz Crystal Microbalances with Dissipation Sensors. (PubMed, Langmuir) - "This study aims at exploring for the first time the influence of electrospun poly(vinyl alcohol)-based nanofibers on the adsorption of a cyclic peptide, Tiger 17, and of a linear peptide, Pexiganan, using quartz crystal microbalance with dissipation monitoring (QCM-D)...Elastic shear modulus data on this peptide sequence, over the C80/20 electrospun mats, reported 220 and 249 kPa for each peptide, respectively, indicating the formation of stable bonds with the surface. The results contributed to the understanding of the immobilization of linear and cyclic peptides, never studied in combination, and their mutual influence on polymeric substrates for engineering potential wound treatment strategies."

Journal

Dhvar5- and MSI78-coated titanium are bactericidal against methicillin-resistant Staphylococcus aureus, immunomodulatory and osteogenic. (PubMed, Acta Biomater) - "The developed coatings displayed MRSA-sterilizing activity, while revealing an immunomodulatory potential towards macrophages and promoting osteoblastic cell differentiation. This strategy allows a quick and easy immobilization of high quantities of AMP, unlike most other approaches, thus favoring its clinical translation."

Immunomodulating • Journal • Immunology • Infectious Disease • Orthopedics • CCR7 • CD163 • IFNG • IL6 • TNFA

Understanding Antimicrobial Peptide Synergy: Differential Binding Interactions and Their Impact on Membrane Integrity. (PubMed, J Phys Chem B) - "In this study, we conducted molecular dynamics simulations for two heterogeneous aggregates of melittin-indolicidin and pexiganan-indolicidin to observe their structures in the solution phase and their interactions with the lipid membrane...We also found that the amino acid residues forming the surface of the AMP aggregate show differential binding strengths to different lipid species forming the lipid membrane, thereby disrupting the membrane in a way that weakens its integrity. Through this, we provided insight into the basic principle of how the synergistic effect of AMPs occurs."

Journal

Evaluation of the activity of antimicrobial peptides against bacterial vaginosis. (PubMed, Open Life Sci) - "The results showed that Pexiganan, melittin, and cathelicidin-DM had significant antibacterial activity against both Gram-negative and Gram-positive bacteria. AMPs have great potential for clinical application in the treatment of vaginitis, and this study provides an experimental basis for their use in the active immunoprophylaxis of BV."

Journal • Gynecology • Infectious Disease • Vaginitis

Testing Synergy of Highly Selective Antimicrobial Peptides Targeting Different Virulence Factors of Helicobacter pylori (ASM Microbe 2024) - "Next, each guide candidate will be added to the AMP, pexiganan...These gAMPs will then be used in combination with gAMPs already produced which target VacA to examine synergistic toxicity against H. pylori. Every combination of anti-CagA gAMP with anti-VacA gAMP will be tested to determine if synergy is possible by assaying for toxicity against H. pylori."

Gastric Cancer • Gastrointestinal Cancer • Infectious Disease • Oncology • Solid Tumor • KEAP1

Sustain-release lipid-liquid crystal formulations of pexiganan against Helicobacter pylori infection: in vitro evaluation in C57BL/6 mice. (PubMed, BMC Pharmacol Toxicol) - "Clarithromycin was more effective than pexiganan at all tested concentrations. Furthermore, the pexiganan-loaded LLCs exhibited superior efficacy in curing H. pylori infection in a mouse model compared to pexiganan alone. This formulation can enhance H. pylori clearance while mitigating the adverse effects, typically associated with conventional drugs, leading to a viable alternative to current treatment options."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Infectious Disease