How Does Membrane Oxidation Affect Cell Delivery and Cell Killing?

Libardo, M. Daben J.; Wang, Ting-Yi; Angeles‐Boza, Alfredo M.

doi:10.1016/j.tibtech.2017.03.015

Cited by 25 publications

(16 citation statements)

References 15 publications

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“…However, based on the observed synergy cases, we assume that membranolytic activity of AMPs plays a certain role in the realization of synergistic interaction. We could also hypothesize, that wide-scale oxidative effects provided by silver compounds can contribute to this outcome, as it has been reported that oxidation of membrane lipids potentiated bactericidal activity of membranoactive AMPs (Libardo et al, 2017).…”

Section: Discussionmentioning

confidence: 89%

Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

Zharkova

Орлов

Golubeva

et al. 2019

Front. Cell. Infect. Microbiol.

197

166

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Rapidly growing resistance of pathogenic bacteria to conventional antibiotics leads to inefficiency of traditional approaches of countering infections and determines the urgent need for a search of fundamentally new anti-infective drugs. Antimicrobial peptides (AMPs) of the innate immune system are promising candidates for a role of such novel antibiotics. However, some cytotoxicity of AMPs toward host cells limits their active implementation in medicine and forces attempts to design numerous structural analogs of the peptides with optimized properties. An alternative route for the successful AMPs introduction may be their usage in combination with conventional antibiotics. Synergistic antibacterial effects have been reported for a number of such combinations, however, the molecular mechanisms of the synergy remain poorly understood and little is known whether AMPs cytotoxicy for the host cells increases upon their application with antibiotics. Our study is directed to examination of a combined action of natural AMPs with different structure and mode of action (porcine protegrin 1, caprine bactenecin ChBac3.4, human alpha- and beta-defensins (HNP-1, HNP-4, hBD-2, hBD-3), human cathelicidin LL-37), and egg white lysozyme with varied antibiotic agents (gentamicin, ofloxacin, oxacillin, rifampicin, polymyxin B, silver nanoparticles) toward selected bacteria, including drug-sensitive and drug-resistant strains, as well as toward some mammalian cells (human erythrocytes, PBMC, neutrophils, murine peritoneal macrophages and Ehrlich ascites carcinoma cells). Using “checkerboard titrations” for fractional inhibitory concentration indexes evaluation, it was found that synergy in antibacterial action mainly occurs between highly membrane-active AMPs (e.g., protegrin 1, hBD-3) and antibiotics with intracellular targets (e.g., gentamicin, rifampcin), suggesting bioavailability increase as the main model of such interaction. In some combinations modulation of dynamics of AMP-bacterial membrane interaction in presence of the antibiotic was also shown. Cytotoxic effects of the same combinations toward normal eukaryotic cells were rarely synergistic. The obtained data approve that combined application of antimicrobial peptides with antibiotics or other antimicrobials is a promising strategy for further development of new approach for combating antibiotic-resistant bacteria by usage of AMP-based therapeutics. Revealing the conventional antibiotics that increase the activity of human endogenous AMPs against particular pathogens is also important for cure strategies elaboration.

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Section: Discussionmentioning

confidence: 89%

Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

Zharkova

Орлов

Golubeva

et al. 2019

Front. Cell. Infect. Microbiol.

197

166

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“…As far as the biological realm is concerned, our results anticipate a strong influence of hydroperoxidation on the interaction of biomembranes with membrane proteins and with membrane-active biomolecules. [46] Indeed, while enrichment of the head region by -OOH groups will likely enhance the affinity of charged species with the membrane, an increased polarity of the inner membrane is expected to facilitate membrane crossing by species such as cell penetrating peptides.…”

Section: Discussionmentioning

confidence: 99%

Molecular organization in hydroperoxidized POPC bilayers

Junqueira

Schröder

Thalmann

et al. 2021

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Lipid hydroperoxides are the primary reaction products of lipid oxidation, a natural outcome of life under oxygen. While playing a major role in cell metabolism, the microscopic origins of the effects of lipid hydroperoxidation on biomembranes remain elusive. Here we probe the polar structure of partially to fully hydroperoxidized bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) by a combination of environment-sensitive fluorescent probes and coarse-grained Martini numerical simulations. We find that the inserted organic hydroperoxide group -OOH migrates preferentially to the surface for bilayers with small fractions of hydroperoxidized lipids, but populates also significantly the bilayer interior for larger fractions. Our findings suggest that by modifying the intimate polarity of biomembranes, lipid peroxidation will have a significant impact on the activity of transmembrane proteins and on the bio-medical efficiency of membrane active molecules such as cell-penetrating and antimicrobial peptides.

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“…In these cases an increased activity by a Cu-ATCUN moiety in AMPs was observed for AMPs proceeding through different mechanisms, suggesting a role for Cu-ATCUN motif not restricted to a single antimicrobial mechanism. It is generally explained by promoting oxidative stress [8,15,[21][22][23]25], whether at the membrane (lipid oxidation) or inside the cell, and or via nucleic acid cleavage [8,20,22,26,27]. Noteworthy, it has been suggested that this nucleic acid cleavage by Cu-ATCUN complexes occurs through an oxidative mechanism [28][29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

Bouraguba

Glattard

Naudé

et al. 2020

Journal of Inorganic Biochemistry

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Depending on the coordination, copper ions can have a very high activity in catalyzing the production of reactive oxygen species. Thus interest arose in increasing the activity of antimicrobial peptides (AMPs) by equipping them with a Cu-binding unit. Several examples, native and engineered, have been investigated with the motif Xxx-Zzz-His, called Amino Terminal Cu(II)-and Ni(II)-binding (ATCUN) motif. Here we investigate a short AMP that was equipped either with Xxx-Zzz-His or Xxx-His. Xxx-His is a shorter motif and yields a more redox active copper complex. The control AMP, Xxx-His-AMP and Xxx-Zzz-His-AMP were investigated toward Cu-binding, Reactive Oxygen Species (ROS) production and antimicrobial activity in E. coli. The data indicate that these Cu-binding motifs have very limited impact on antimicrobial activity and low ROS production capability.

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How Does Membrane Oxidation Affect Cell Delivery and Cell Killing?

Cited by 25 publications

References 15 publications

Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

Molecular organization in hydroperoxidized POPC bilayers

Copper-binding motifs Xxx-His or Xxx-Zzz-His (ATCUN) linked to an antimicrobial peptide: Cu-binding, antimicrobial activity and ROS production

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