Deciphering the Limitations and Antibacterial Mechanism of Cruzioseptins

Valdivieso-Rivera, Fernando; Bermúdez-Puga, Sebastián; Proaño-Bolaños, Carolina; Almeida, José R.

doi:10.1007/s10989-022-10383-4

Cited by 7 publications

(2 citation statements)

References 47 publications

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“…The experimental protocol described by Valdivieso-Rivera et al [83] was employed to visualise changes in bacterial cell permeability induced by Chenopodin-derived molecules. Peptide dilutions were made using MIC concentrations that had been determined previously and cultured with log-phase bacteria for 30 min before centrifugation at 3000× g for 15 min.…”

Section: Insights Into the Mechanism Of Action 441 Fluorescence Micro...mentioning

confidence: 99%

Antibacterial and Antiviral Properties of Chenopodin-Derived Synthetic Peptides

Feijoo-Coronel,

Mendes,

Ramírez

et al. 2024

Antibiotics

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Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an Andean plant with high nutritional and therapeutic properties. Here, we used computer- and physicochemical-based strategies and designed four peptides derived from the primary structure of Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1 does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are assembled in the membrane. Whereas, some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides.

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Section: Insights Into the Mechanism Of Action 441 Fluorescence Micro...mentioning

confidence: 99%

Antibacterial and Antiviral Properties of Chenopodin-Derived Synthetic Peptides

Feijoo-Coronel,

Mendes,

Ramírez

et al. 2024

Antibiotics

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“…The antimicrobial mechanism of natural and engineered cruzioseptins on Staphylococcus aureus, Escherichia coli , and Leishmania spp. seems to involve the electrostatic interaction and consequently disrupting of cell membrane ( Mendes et al, 2020 ; Valdivieso-Rivera et al, 2022 ; Bermúdez-Puga et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Dual antibacterial mechanism of [K4K15]CZS-1 against Salmonella Typhimurium: a membrane active and intracellular-targeting antimicrobial peptide

Bermúdez-Puga,

Dias,

Freire de Oliveira

et al. 2023

Front. Microbiol.

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Salmonella genus is a leading cause of food-borne infections with strong public health impact and economic ramifications. The development of antimicrobial resistance added complexity to this scenario and turned the antibiotic drug discovery into a highly important challenge. The screening of peptides has served as a successful discovery platform to design new antibiotic candidates. Motivated by this, the antimicrobial and cytotoxic properties of three cruzioseptins against Salmonella Typhimurium and RAW 264.7 murine macrophage cells, respectively, were investigated. [K4K15]CZS-1 was the most potent antimicrobial peptide identified in the screening step with a minimum inhibitory concentration (MIC) of 16 μg/mL (7.26 μM) and moderate cytotoxicity. From a structural point of view, in vitro and in silico techniques evidenced that [K4K15]CZS-1 is a α-helical cationic antimicrobial peptide. In order to capture mechanistic details and fully decipher their antibacterial action, we adopted a multidimensional approach, including spectroscopy, electron microscopy and omics analysis. In general lines, [K4K15]CZS-1 caused membrane damage, intracellular alterations in Salmonella and modulated metabolic pathways, such as the tricarboxylic acid (TCA) cycle, fatty acid biosynthesis, and lipid metabolism. Overall, these findings provide deeper insights into the antibacterial properties and multidimensional mode of action of [K4K15]CZS-1 against Salmonella Typhimurium. In summary, this study represents a first step toward the screening of membrane-acting and intracellular-targeting peptides as potential bio-preservatives to prevent foodborne outbreaks caused by Salmonella.

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