# Developing antibacterial peptides as a promising therapy for combating antibiotic-resistant Pseudomonas aeruginosa infections

**Authors:** Rula M. Darwish, Ali H. Salama

PMC · DOI: 10.14202/vetworld.2024.1259-1264 · Veterinary World · 2024-06-08

## TL;DR

This study explores a new peptide, KW-23, that effectively fights drug-resistant Pseudomonas aeruginosa with low toxicity.

## Contribution

The novel contribution is the development and evaluation of the antibacterial peptide KW-23 against antibiotic-resistant Pseudomonas aeruginosa.

## Key findings

- KW-23 showed strong antibacterial activity against multidrug-resistant P. aeruginosa with an MIC of 20 μg/mL.
- KW-23 combined with gentamicin exhibited synergistic effects against resistant P. aeruginosa.
- KW-23 demonstrated low hemolytic toxicity and rapid antibacterial action.

## Abstract

Antibiotic-resistant Pseudomonas aeruginosa poses a serious health threat. This study aimed to investigate the antibacterial activity of peptide KW-23 against drug-resistant P. aeruginosa and its potential for enhancing the efficacy of conventional antibiotics.

KW-23 was synthesized from nine amino acids, specifically three tryptophans and three lysines. The purity of the substance was analyzed using reverse-phase high-performance liquid chromatography. The peptide was identified through mass spectrometry using electrospray ionization. The minimum inhibitory concentration (MIC) values of KW-23 in combination with conventional antibiotics against control and multidrug-resistant P. aeruginosa were determined utilizing broth microdilution. The erythrocyte hemolytic assay was used to measure toxicity. The KW-23 effect was analyzed using the time-kill curve.

The peptide exhibited strong antibacterial activity against control and multidrug-resistant strains of P. aeruginosa, with MICs of 4.5 μg/mL and 20 μg/mL, respectively. At higher concentration of 100 μg/mL, KW-23 exhibited a low hemolytic impact, causing no more than 3% damage to red blood. The cytotoxicity assay demonstrates KW-23’s safety, while the time-kill curve highlights its rapid and sustained antibacterial activity. The combination of KW-23 and gentamicin exhibited synergistic activity against both susceptible and resistant P. aeruginosa, with fractional inhibitory concentration index values of 0.07 and 0.27, respectively.

The KW-23 synthesized in the laboratory significantly combats antibiotic-resistant P. aeruginosa. Due to its strong antibacterial properties and low toxicity to cells, KW-23 is a promising alternative to traditional antibiotics in combating multidrug-resistant bacteria.

## Linked entities

- **Chemicals:** gentamicin (PubChem CID 3467)
- **Species:** Pseudomonas aeruginosa (taxon 287)

## Full-text entities

- **Diseases:** Pseudomonas aeruginosa infections (MESH:D011552), cytotoxicity (MESH:D064420), hemolytic (MESH:D006461)
- **Chemicals:** amino acids (MESH:D000596), lysines (MESH:D008239), gentamicin (MESH:D005839), tryptophans (MESH:D014364), KW-23 (-)
- **Species:** Pseudomonas aeruginosa (species) [taxon 287], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]

## Full text

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## Figures

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## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC11283607/full.md

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Source: https://tomesphere.com/paper/PMC11283607