BamA-targeted antimicrobial peptide design for enhanced efficacy and reduced toxicity

Yang, Li; Luo, Minghe; Liu, Zhou; Li, Yuepeng; Lin, Zhihua; Geng, Shan; Wang, Yuanqiang

doi:10.1007/s00726-023-03307-z

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…These advantages enable them to hold great promise as the most potential alternatives to conventional antibiotics. Nevertheless, their high toxic and hemolytic properties limit their practical applications ( Oddo and Hansen, 2017 ; Yang et al., 2023 ). Due to the diversity of antimicrobial mechanisms, the mechanism of antimicrobial peptides is still unclear.…”

Section: Introductionmentioning

confidence: 99%

The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli

Tian,

Zhao,

Yang

et al. 2024

Front. Cell. Infect. Microbiol.

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IntroductionBacterial infections have become serious threats to human health, and the excessive use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria. E. coli is a human bacterial pathogen, which can cause severe infectious. Antimicrobial peptides are considered the most promising alternative to traditional antibiotics.Materials and methodsThe minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and hemolytic activity were determined by the microdilution method. The antimicrobial kinetics of MR-22 against E. coli were studied by growth curves and time-killing curves. The cytotoxicity of MR-22 was detected by the CCK-8 assay. The antimicrobial activity of MR-22 in salt, serum, heat and trypsin was determined by the microdilution method. The antimicrobial mechanism of MR-22 against drug-resistant E. coli was studied by Scanning Electron Microscope, laser confocal microscopy, and Flow Cytometry. The in vivo antibacterial activity of MR-22 was evaluated by the mice model of peritonitis.Results and discussionIn this study, MR-22 is a new antimicrobial peptide with good activity that has demonstrated against MDR E. coli. The antimicrobial activity of MR-22 exhibited stability under conditions of high temperature, 10% FBS, and Ca2+. However, a decline of the activity was observed in the presence of Na+, serum, and trypsin. MR-22 had no significant cytotoxicity or hemolysis in vitro. SEM and fluorescent images revealed that MR-22 could disrupt the integrity of cell membrane. DCFH-DA indicated that MR-22 increased the content of reactive oxygen species, while it decreased the content of intracellular ATP. In mice model of peritonitis, MR-22 exhibited potent antibacterial activity in vivo. These results indicated that MR-22 is a potential drug candidate against drug-resistant E. coli.

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Section: Introductionmentioning

confidence: 99%

The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli

Tian,

Zhao,

Yang

et al. 2024

Front. Cell. Infect. Microbiol.

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Antimicrobial activity of novel symmetrical antimicrobial peptides centered on a hydrophilic motif against resistant clinical isolates: in vitro and in vivo analyses

Zhang,

Fu,

Zhu

et al. 2024

Microbiol Spectr

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Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine–serine–glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W 5 demonstrated a rapid and effective sterilization against methicillin-resistant Staphylococcus aureus (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W 5 killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W 5 also exhibited excellent biocompatibility in both in vitro and in vivo safety evaluations. AMP W 5 treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections. IMPORTANCE Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine–serine–glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications.

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Antibiotics-free compounds for managing carbapenem-resistant bacteria; a narrative review

Shariati,

Kashi,

Chegini

et al. 2024

Front. Pharmacol.

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Carbapenem-resistant (CR) Gram-negative bacteria have become a significant public health problem in the last decade. In recent years, the prevalence of CR bacteria has increased. The resistance to carbapenems could result from different mechanisms such as loss of porin, penicillin-binding protein alteration, carbapenemase, efflux pump, and biofilm community. Additionally, genetic variations like insertion, deletion, mutation, and post-transcriptional modification of corresponding coding genes could decrease the susceptibility of bacteria to carbapenems. In this regard, scientists are looking for new approaches to inhibit CR bacteria. Using bacteriophages, natural products, nanoparticles, disulfiram, N-acetylcysteine, and antimicrobial peptides showed promising inhibitory effects against CR bacteria. Additionally, the mentioned compounds could destroy the biofilm community of CR bacteria. Using them in combination with conventional antibiotics increases the efficacy of antibiotics, decreases their dosage and toxicity, and resensitizes CR bacteria to antibiotics. Therefore, in the present review article, we have discussed different aspects of non-antibiotic approaches for managing and inhibiting the CR bacteria and various methods and procedures used as an alternative for carbapenems against these bacteria.

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BamA-targeted antimicrobial peptide design for enhanced efficacy and reduced toxicity

Cited by 3 publications

References 43 publications

The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli

The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli

Antimicrobial activity of novel symmetrical antimicrobial peptides centered on a hydrophilic motif against resistant clinical isolates: in vitro and in vivo analyses

Antibiotics-free compounds for managing carbapenem-resistant bacteria; a narrative review

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