- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Journal: Evolutionary trajectory of bacterial resistance to antibiotics and antimicrobial peptides in Escherichia coli. (Pubmed Central) - Feb 27, 2025
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.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Journal: 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 Central) - Dec 17, 2024
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.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Journal: Understanding Antimicrobial Peptide Synergy: Differential Binding Interactions and Their Impact on Membrane Integrity. (Pubmed Central) - Sep 30, 2024
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.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Journal: Evaluation of the activity of antimicrobial peptides against bacterial vaginosis. (Pubmed Central) - Aug 2, 2024
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.
- |||||||||| omiganan (CLS001) / Maruho, Locilex (pexiganan acetate) / PLx Pharma
Review, Journal: Rational design of stapled antimicrobial peptides. (Pubmed Central) - May 1, 2023
P3
Antimicrobial peptides under clinical trial: Pexiganan (NCT01594762, 2012-05-07). Omiganan (NCT02576847, 2015-10-13).
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Journal: Peptide Flexibility and the Hydrophobic Moment are Determinants to Evaluate the Clinical Potential of Magainins. (Pubmed Central) - Apr 25, 2023
The flexibility of another magainin analog (MSI-78) is even greater than that of Mag-2...Such characteristics are key to understanding the broad-spectrum antimicrobial actions exhibited by this peptide. These data reinforce the hypothesis on the determinant role of spontaneous membrane curvature, intrinsic peptide flexibility, and specific hydrophobic moment in assessing the bioactivity of membrane-active antimicrobial peptides.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Journal: The Impact of Antimicrobial Peptides on the Acinetobacter baumannii Inner Membrane Is Modulated by Lipid Polyunsaturation. (Pubmed Central) - Apr 17, 2023
Using coarse-grained molecular dynamics simulations of complex A. baumannii inner membrane models derived from lipidomes of bacteria grown in the presence and absence of PUFAs, we examine the impact of the adsorption of four prototypical AMPs (CAMEL, LL-37, pexiganan, and magainin-2) on the membrane biophysical properties...The changes to the membrane biophysical properties also showed a complex relationship with the AMP's physical properties, such as AMP charge, chain length, and charge-to-mass ratio. Cumulatively, this work highlights the importance of studying AMPs using a complex membrane environment and provides insights into the mechanistic action of AMPs in polyunsaturated lipid-rich bacterial membranes.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Evaluation of the efficacy of the antimicrobial peptide HJH-3 in chickens infected with Salmonella Pullorum. (Pubmed Central) - Feb 11, 2023
The prevention of infection by HJH-3 was similar to that by Ampicillin; the effect of treatment after infection was lower than that of treatment before infection, and the survival rate of infected chicks treated with HJH-3 was 70%, which was still higher than that of the infected chickens. These results suggest that HJH-3 has good clinical application potential and can be used as a substitute for antibiotics for the prevention and treatment of S. Pullorum infection.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections. (Pubmed Central) - Dec 3, 2022
NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition...Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Formulation and Biological Evaluation of Mesoporous Silica Nanoparticles Loaded with Combinations of Sortase A Inhibitors and Antimicrobial Peptides. (Pubmed Central) - May 30, 2022
A resazurin-modified minimum inhibitory concentration (MIC) and checkerboard assays, to measure SrtAI synergy in combination with leading antimicrobial peptides (AMPs; pexiganan (PEX), indolicidin (INDO), and [I5, R8] mastoparan (MASTO)), were determined against methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa...These combinations also reduced each components' toxicity against human embryonic kidney cells. In conclusion, MCM-41 MSNs provide a platform to enhance SrtAI solubility and demonstrated antimicrobial synergy with AMPs and reduced toxicity, providing novel superbug treatment opportunities.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Review, Journal: Antimicrobial Peptide Mechanisms Studied by Whole-Cell Deuterium NMR. (Pubmed Central) - Apr 9, 2022
This review focusses on what can be learned about AMP mechanisms from solid-state NMR of AMP-treated intact bacteria. It also touches on flow cytometry as a complementary method for measuring permeabilization of bacterial lipid membranes in whole bacteria.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Systematic comparison of activity and mechanism of antimicrobial peptides against nosocomial pathogens. (Pubmed Central) - Mar 4, 2022
This study demonstrated a structure and activity guidance for further design of Pardaxin (1-22) and MSI-78 (4-20) as therapeutics against MDR pathogens. The different effects of DMPC (1-19) and Cecropin B (1-21) on membrane integrity and phospholipid membrane interactions provided critical information for the rational design of next-generation analogues with specificity against either Gram-negative or Gram-positive bacteria.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Preclinical, Journal: In vitro activity of the antimicrobial peptides h-Lf1-11, MSI-78, LL-37, fengycin 2B, and magainin-2 against clinically important bacteria. (Pubmed Central) - Mar 3, 2022
The h-Lf1-11, magainin-2, and LL-37 exhibited moderate activity (MIC range of 40-160, 80-160, and 40-160 mg/L, respectively) while the fengycin 2B did not show significant activity against all bacterial strains tested. These results revealed that MSI-78, h-Lf1-11, magainin-2, and LL-37 have great potential as antibacterial agents and their activity deserves to be more explored in further studies for the treatment of antibiotic-resistant bacteria.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Anti-Pythium insidiosum activity of MSI-78, LL-37, and magainin-2 antimicrobial peptides. (Pubmed Central) - Mar 3, 2022
Antimicrobial peptides were tested against Pythium insidiosum, a microorganism that causes a difficult-to-treat disease in animals and humans. These peptides have been shown to be able to kill P. insidiosum and may be candidates for use in the treatment of this infection.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Grafting MSI-78A onto chitosan microspheres enhances its antimicrobial activity. (Pubmed Central) - Jan 27, 2022
MSI-78A (Pexiganan A) is one of the few antimicrobial peptides (AMPs) able to kill Helicobacter pylori, a pathogenic bacterium that colonizes the gastric mucosa of half of the world's population...pylori activity even at acidic pH (gastric settings). These results highlight the strong potential of AMP-ChMic as an antibiotic alternative for H. pylori eradication.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Helicity modulation improves selectivity of antimicrobial peptoids. (Pubmed Central) - Jun 24, 2021
Compared to pexiganan AMP, 17 showed superior metabolic stability, which could potentially reduce the dosage needed, alleviating toxicity...However, the high selectivity of 17 reflected its unique conformational characteristics, with differential interactions between bacterial and erythrocyte membranes. Our results suggest a way to distinguish different membrane compositions solely by helicity modulation, thereby improving selectivity toward bacterial cells with the maintenance of potent and broad-spectrum activity.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Switching Bond: Generation of New Antimicrobial Peptides via the Incorporation of an Intramolecular Isopeptide Bond. (Pubmed Central) - Jun 24, 2021
To overcome these challenges, we herein replaced the regular peptide bonds with isopeptide bonds to produce new AMPs based on the well-known synthetic peptides Amp1L and MSI-78 (pexiganan)...Their mode of action, assessed by flow cytometry, includes permeabilization of the bacterial membrane. Overall, we present here a new approach to modulate AMPs to develop antimicrobial peptides for future therapeutic purposes.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Antibacterial nanotruffles for treatment of intracellular bacterial infection. (Pubmed Central) - May 15, 2021
To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles...Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Antimicrobial Peptide Induced-Stress Renders Staphylococcus aureus Susceptible to Toxic Nucleoside Analogs. (Pubmed Central) - Apr 14, 2021
We then show that Staphylococcus aureus is highly susceptible to antimetabolite nucleoside analogs when exposed to pexiganan, even at sub-inhibitory concentrations. These findings could be used to enhance pexiganan potency while decreasing the risk of resistance emergence, and our findings can likely be extended to other antimicrobial peptides.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Potent antibacterial activity of MSI-1 derived from the magainin 2 peptide against drug-resistant bacteria. (Pubmed Central) - Apr 10, 2021
Here, we truncated 14-amino-acids at the N-terminus of MSI-78 to obtain MSI and further modified MSI to obtain four peptide analogs: MSI-1, MSI-2, MSI-3 and MSI-4...In terms of the mode of action, we found that at the super-MIC level, MSI-1 exhibited direct antimicrobial activity by disrupting the integrity of the bacterial cell membrane, while at the sub-MIC level, it bound to bacterial DNA to inhibit DNA replication and protein expression and ultimately disrupted bacterial biological function. This novel peptide MSI-1 could be a potential candidate for drug development against infection induced by drug-resistant bacteria.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: AMP-Chitosan Coating with Bactericidal Activity in the Presence of Human Plasma Proteins. (Pubmed Central) - Mar 27, 2021
The MSI-78(4-20)-chitosan coating demonstrated bactericidal properties independently of the tethering site and an improved performance in the presence of plasma proteins, which mimics conditions that will be encountered in vivo. This AMP-chitosan coating has therefore great potential for applications in medical devices such as implants or even wound dressings.
- |||||||||| rifampicin / Generic mfg.
Journal: SAAP-148 Eradicates MRSA Persisters Within Mature Biofilm Models Simulating Prosthetic Joint Infection. (Pubmed Central) - Feb 17, 2021
Bacteria obtained from and residing within these biofilms were exposed to SAAP-148, acyldepsipeptide-4, LL-37, and pexiganan...SAAP-148 is highly effective against persisters obtained from the biofilms as well as within these models. Antibiotics-exposed, mature biofilms on relevant surfaces can be instrumental in the search for novel treatment strategies to combat biofilm-associated infections.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Short communication: Algaecide activity of antimicrobial peptides compounds against Prototheca bovis. (Pubmed Central) - Jan 20, 2021
The minimum inhibitory concentration ranged from 5 to 10 µg/mL for pexiganan, and algaecide effect was detected from 5 to 20 µg/mL. The minimum inhibitory concentration ranged from 10 to 80 µg/mL for h-Lf1-11, 20 to 80 µg/mL for LL-37, and 40 to 160 µg/mL for cecropin B. These findings present a promising and novel alternative for P. bovis treatment and growth control.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Effect of AMPs MSI-78 and BP100 on the Lipid Acyl Chains of H-Labeled Intact Gram Positive Bacteria. (Pubmed Central) - Sep 13, 2020
In addition, the peptide to lipid molar ratios (P:L) that give rise to observable effects fall between the P:L molar ratios necessary to generate membrane disruption in model-lipid-only systems and the P:L molar ratios needed to inhibit bacterial cell growth. This observation supports a role for the non-lipid components in modulating the AMP-lipid interactions.
- |||||||||| vancomycin / Generic mfg., Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Activity of Specialized Biomolecules against Gram-Positive and Gram-Negative Bacteria. (Pubmed Central) - Jun 13, 2020
The antibiotic vancomycin and silver nanoparticles (AgNPs) were used as control compounds for comparison purposes...AMPs were observed to induce morphological deformations and cellular content release, while EOs were seen to split and completely envelope bacteria. Data unraveled more of the potential of these new biomolecules as replacements for the conventional antibiotics and allowed us to take a step forward in the understanding of their mechanisms of action against infection-related bacteria.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal: Localization Preference of Antimicrobial Peptides on Liquid-Disordered Membrane Domains. (Pubmed Central) - Jun 9, 2020
We performed coarse-grained simulations of the antimicrobial peptides Magainin-2, BP100, MSI-103, and MSI-78 on a phase-separated membrane to study their preference for the different domains...Interestingly, at high concentrations of Magainin-2 toroidal pores spontaneously formed in the Ld phase. We performed additional simulations to characterize this phenomenon, which is likely related to Magainin-2's membranolytic action.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Journal, Combination therapy: Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections. (Pubmed Central) - Apr 6, 2020
Importantly, the application of the dual-AMP biogel resulted in the eradication of the S. aureus strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Preclinical, Journal: In Vitro Efficiency of Antimicrobial Peptides against Staphylococcal Pathogens Associated with Canine Pyoderma. (Pubmed Central) - Mar 16, 2020
Seven antimicrobial peptides (aurein 1.2, CAMEL, citropin 1.1, protegrin-1, pexiganan, temporin A and uperin 3.6) synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase method were tested...The tested AMPs were equally efficient against both resistant- and susceptible staphylococcal strains and were more efficient against Staphylococcus pseudintermedius than against Staphylococcus aureus strains. Our findings are particularly interesting from a clinical perspective, as they point to AMPs as potential therapeutic topical agents in canine pyoderma cases associated with antimicrobial resistance of staphylococci.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
PK/PD data, Journal: Resistance Evolution Against Antimicrobial Peptides in Staphylococcus aureus Alters Pharmacodynamics Beyond the MIC. (Pubmed Central) - Mar 3, 2020
aureus selected for resistance to melittin displayed cross resistant against pexiganan and had as steep pharmacodynamic curves (high κ) as pexiganan-selected lines...Taken together, our data demonstrate that pharmacodynamic parameters are not fixed traits of particular drug/strain interactions but actually evolve under drug treatment. The contribution of factors such as κ and the maximum and minimum growth rates on the dynamics and probability of resistance evolution are open questions that require urgent attention.
- |||||||||| Silverzine Tulle (Silver Sulfadiazine) / MinaPharm, mupirocin / Generic mfg., Locilex (pexiganan acetate) / PLx Pharma Inc
Clinical, Journal: SPS-neutralization in tissue samples for efficacy testing of antimicrobial peptides. (Pubmed Central) - Feb 25, 2020
The contribution of factors such as κ and the maximum and minimum growth rates on the dynamics and probability of resistance evolution are open questions that require urgent attention. SPS was successfully used to neutralize residual activity of SAAP-148, pexiganan and chlorhexidine and this prevented an overestimation of their efficacy.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma Inc
Activity and distribution of the antimicrobial peptides nisin and pexiganan in a diabetic foot infection 3D model () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_2135;
The development of topical therapeutic protocols combining different AMPs, namely pexiganan and nisin, and conventional antibiotics could be a solution for the treatment of recalcitrant DFU infections, particularly those caused by biofilm-forming multidrug-resistant pathogens. The dual-AMP biogel topical application may represent a promising alternative or complement to antibiotic-based therapy for DFI treatment, but further studies are required to improve the biogel antibacterial activity aiming at eradicating all DFI-related pathogens and also biofilms.
- |||||||||| Locilex (pexiganan acetate) / PLx Pharma
Trial completion, Head-to-Head: OneStep-2: Pexiganan Versus Placebo Control for the Treatment of Mild Infections of Diabetic Foot Ulcers (clinicaltrials.gov) - Aug 10, 2016
P3, N=200, Completed,
The dual-AMP biogel topical application may represent a promising alternative or complement to antibiotic-based therapy for DFI treatment, but further studies are required to improve the biogel antibacterial activity aiming at eradicating all DFI-related pathogens and also biofilms. Recruiting --> Completed
|
