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Developing antibacterial peptides as a promising therapy for combating antibiotic-resistant Pseudomonas aeruginosa
Rula M Darwish1, Ali H Salama2
1Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, the University of Jordan, Amman, 11942, Jordan.
Background And Aim:
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.
Materials And Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Peptide KW-23 shows strong antibacterial activity against antibiotic-resistant Pseudomonas aeruginosa. This peptide is a promising alternative to traditional antibiotics for combating multidrug-resistant bacteria.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Antibiotic-resistant *Pseudomonas aeruginosa* presents a significant global health challenge.
- The emergence of multidrug-resistant strains necessitates novel therapeutic strategies.
Purpose of the Study:
- To evaluate the antibacterial efficacy of synthesized peptide KW-23 against drug-resistant *P. aeruginosa*.
- To investigate the potential of KW-23 in enhancing the activity of conventional antibiotics.
Main Methods:
- Peptide KW-23 synthesis and characterization (HPLC, mass spectrometry).
- Determination of minimum inhibitory concentration (MIC) via broth microdilution.
- Assessment of cytotoxicity using erythrocyte hemolytic assay and time-kill kinetics.
Main Results:
- KW-23 demonstrated potent activity against *P. aeruginosa* strains (MICs 4.5–20 μg/mL) with low hemolytic impact (<3% at 100 μg/mL).
- Synergistic effects observed when KW-23 was combined with gentamicin against susceptible and resistant *P. aeruginosa*.
- Time-kill assays confirmed rapid and sustained antibacterial action of KW-23.
Conclusions:
- Laboratory-synthesized KW-23 effectively combats antibiotic-resistant *P. aeruginosa*.
- KW-23's favorable safety profile and potent antibacterial properties position it as a promising candidate for treating multidrug-resistant infections.
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