The interaction of antimicrobial peptides with membranes

Travkova, Oksana G.; Moehwald, Helmuth; Brezesinski, Gerald

doi:10.1016/j.cis.2017.06.001

Cited by 159 publications

(125 citation statements)

References 129 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…Membrane permeabilization is the most common mechanism of antimicrobial peptide action. Researchers have proposed multiple models of peptides interacting with membranes . Based on our data, we have an interesting finding that zp3 seems to be more likely to attack the central region of the bacterial cell.…”

Section: Resultsmentioning

confidence: 63%

“…Researchersh ave proposed multiple modelso fp eptides interacting with membranes. [36,42] Based on our data, we have an interesting finding that zp3 seemst ob em ore likely to attack the central region of the bacterial cell. In STEM images, we observed clear substance accumulation at the cell poles ( Figure 8A).…”

Section: Zp3 Showshigher Affinity For the Bacterial Cell Center And Lmentioning

confidence: 62%

“…Antibacterial compounds can be classified into two groups: bacteriostatic and bactericidal agents. Most antimicrobial peptides disrupt cell membrane integrity by forming pores and gaining access to the cytoplasm . This process causes a series of physiological changes.…”

Section: Resultsmentioning

confidence: 99%

“…Most antimicrobial peptides disrupt cell membrane integrity by forming pores and gaining access to the cytoplasm. [36] This process causes as eries of physiological changes.T he morphological abnormalities of bacteria after treatment with thesep eptides has been observedb yar ange of microscopic approaches. [18a, 20] Broadly speaking, antimicrobial peptidesa re more effective against bacteria than small organic molecules because they quickly recognize the negatively charged surface of the bacterial membrane and attack the phospholipid layer.A ss hown in Fig We then investigated the cytotoxicity of zp3.H EK293 (human embryonic kidney) cells were used for in vitro testing by MTT assay.C ells were pre-incubated for2 4h.A fter another 24 hofpeptide treatment, the survival rate wascalculated relative to the control group.…”

Section: Zp3 Showslow Toxicity and Performs Well In Ahigh-salt Enviromentioning

confidence: 99%

See 3 more Smart Citations

Phenol‐Soluble‐Modulin‐Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug‐Resistant Bacteria

et al. 2019

View full text Add to dashboard Cite

Phenol‐soluble modulins (PSMs) are a large family of cytolytic peptide toxins produced by Staphylococcus aureus. Based on their amino acid sequences, we have constructed a small library of cationic isoleucine‐rich peptides for antimicrobial evaluation. Relative to the parent PSMs, peptide zp3 (GIIAGIIIKIKK‐NH2) was found to possess greatly improved physicochemical properties (soluble in water) and antibacterial activity (MIC=8 μm for E. coli, B. subtilis, and C. freundii) while maintaining low hemolytic activity (<5 % at 256 μm) and cytotoxicity (HEK293 cells IC50>80 μm). We reasoned that the selective activity of zp3 toward bacterial cells is due to its amphiphilic nature and positive net charge. Moreover, it is difficult for bacteria to develop resistance against zp3. Through microscopic studies of E. coli, we demonstrated that zp3 can penetrate the bacterial membrane, thereby causing leakage of the bacterial cytoplasm. Our findings present a promising antimicrobial peptide lead, which has great potential for further chemical modification.

show abstract

Section: Resultsmentioning

confidence: 63%

Section: Zp3 Showshigher Affinity For the Bacterial Cell Center And Lmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Zp3 Showslow Toxicity and Performs Well In Ahigh-salt Enviromentioning

confidence: 99%

See 2 more Smart Citations

Phenol‐Soluble‐Modulin‐Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug‐Resistant Bacteria

et al. 2019

View full text Add to dashboard Cite

show abstract

“…LPS from E. coli and other gram-negative bacteria is the endotoxin and activates innate immunity through binding TLR4 receptors [39]. The overall positive charge on cationic antimicrobial peptides assists them to form strong electrostatic interactions with the negatively charged LPS in the membrane of Gram-negative bacteria neutralizing the overall negative charge [40, 41]. The binding of cationic antimicrobial peptides with LPS of Gram-negative bacteria has a major effect on the stability of bacterial membranes.…”

Section: Resultsmentioning

confidence: 99%

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Hoek

Kaushal

Bishop

et al. 2019

Preprint

View full text Add to dashboard Cite

7Our long-term goal is to identify new antimicrobial peptides that might be effective 8 against pneumonic Francisella infection in mice. Previously, our group searched the peptidome 9 of the American alligator for novel cationic antimicrobial peptides and identified a naturally-10 occurring C-terminal fragment of apolipoprotein C-1, which we called Apo6. This peptide was 11 found to have antibacterial activity against the ESKAPE pathogens, including those exhibiting 12 multi-drug resistance. In this work, we tested Apo6 and synthetic derivatives for antibacterial 13 activity against Francisella tularensis including the virulent strain F. tularensis SchuS4.14 Francisella is inherently highly resistant to the cyclic peptide polymyxin antibiotics and beta-15 lactam antibiotics. We found that our synthetic peptide derivatives (called GATR peptides), 16 designed with increased hydrophobicity and charge, had generally stronger in vitro antimicrobial 17 activity against Francisella than the parent peptide Apo6. The GATR peptides had a greater 18 effect on the bacterial membrane than the Apo6 peptide and were able to bind Francisella LPS, 19 suggesting their mechanism of action against Francisella. Cytotoxicity experiments showed low 20 cytotoxicity for most of the GATR peptides, and whole organism toxicity studies in the 21 waxworm allowed us to down-select to two our lead peptides, GATR-3 and GATR-6. These 22 peptides were tested in a murine pulmonary tularemia model. We found that the GATR-3 peptide 23 rescued 50-60% of mice from lethal tularemia infection when administered systemically through 24 2 the intraperitoneal route. This peptide is a candidate for further pre-clinical studies for a potential 25 peptide-based approach to tularemia. 26

show abstract

Conformational Transition‐Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy

Wang

Yang

Hou

et al. 2021

Adv Healthcare Materials

View full text Add to dashboard Cite

Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged α‐helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep‐HCO3 modified with bicarbonates on guanidine groups is designed. Such a design allows Pep‐HCO3 ((nap‐RAGLQFPVGRLLRRLLRRLLR) nHCO3) to self‐assemble into nanoparticles (NP‐Pep) due to disrupting helix folding and the formation of intermolecular hydrogen bonding between bicarbonates and guanidine groups. When pH is from 7.4 to 6.5 at the tumor sites, guanidine bicarbonate can be hydrolyzed to form CO2 and guanidine groups, resulting in the disassembling of the NP‐Pep into monomers α‐Pep with a positively charged α‐helix structure. In vivo, NP‐Pep not only inhibits the tumor growth of xenografted mice with a twofold enhanced inhibition rate compared with α‐Pep treatment group, but also significantly reduces the hemolytic toxicity by responding to the pH of tumor microenvironment. Therefore, the strategy of conformational transition‐triggered disassembly of nanoparticles allows efficient delivery of cationic therapeutic peptides and lowering the hemolytic toxicity, which may provide an avenue for developing high‐performance cationic peptide in vivo applications.

show abstract

The interaction of antimicrobial peptides with membranes

Cited by 159 publications

References 129 publications

Phenol‐Soluble‐Modulin‐Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug‐Resistant Bacteria

Phenol‐Soluble‐Modulin‐Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug‐Resistant Bacteria

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Conformational Transition‐Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy

Contact Info

Product

Resources

About