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

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.

A pilot study on ultrashort peptide with fluconazole: A promising novel anticandidal combination.

Background and Aim: Human infections caused by Candida albicans are common and range in severity from relatively treatable skin and mucosal conditions to systemic, fatal invasive candidiasis. The treatment of fungal infections is challenged by major obstacles, including the scarcity of effective therapeutic options, the toxicity of available medications, and the escalating antifungal resistance. Hence, there exists an urgent need to develop new classes of antimicrobial agents. This study was conducted to investigate the effect of KW-23 peptide against standard and resistant strains of C. albicans alone and in combination with fluconazole. Materials and Methods: A conjugated ultrashort antimicrobial peptide (KW-23) was designed and synthesized. KW-23 was challenged against standard and multidrug-resistant C. albicans alone and in combination with fluconazole using standard antimicrobial and checkerboard assays. The toxicity of the peptide was examined using hemolytic assays. Results: KW-23 positively affected the standard and resistant Candidal strains (at 5 and 15 µg/mL respectively), exhibiting potent synergistic antimicrobial activity against the standard strain when combined with fluconazole. The effect of the combination was additive against the resistant strain (0.6 µg/mL). Furthermore, the peptide exhibited negligible toxicity on human erythrocytes. Conclusion: KW-23 and its combination with fluconazole could be a promising candidate for developing anticandidal agents.

Study the Effect of Conjugate Novel Ultra-Short Antimicrobial Peptide with Silver Nanoparticles against Methicillin Resistant S. aureus and ESBL E. coli.

Background: Bacterial resistance is a challenging limitation in infection treatment. This work evaluates the potential antibacterial activity of conjugation of Tryasine peptide with silver nanoparticles against selected pathogens. Materials and Methods: The peptide Tryasine was produced using three subunits of tryptophan and three lysine amino acids, then its purity was determined by reverse-phase high-performance liquid chromatography. The peptide was confirmed using mass spectrometry and electrospray ionization mass spectrometry. Silver nanoparticles conjugate with Tryasine was synthesized by adding Tryasine-silver nitrate solution in the presence of the reducing agent sodium borohydride. The presence of Tryasine-silver nanoparticles was indicated by the yellow-brown color and was further confirmed through ultraviolet-visible spectrophotometry. The minimum inhibitory and minimum bactericidal concentrations for Tryasine nanoparticles were determined against Staphylococcus aureus, Escherichia coli, methicillin resistant Staphylococcus aureus, and ESBL Escherichia coli using the microdilution method. Toxicity for nanoparticles conjugated with Tryasine was determined using erythrocyte hemolytic assay. Results: Tryasine alone was effective (MIC around 100 and 200 µM) against standard and resistant strains of bacteria used. However, Tryasine-silver nanoparticles were more effective with MICs ranging from 30 to 100 µM depending on the bacterial strain used. Tryasine-silver nanoparticles at concentration of 100 µM only caused 1% hemolysis on human erythrocytes after 30 min of incubation. Conclusions: The findings indicate that Tryasine-silver nanoparticles had good antibacterial activity against pathogenic strains of Gram-positive and Gram-negative bacteria. Additionally, the conjugate showed low hemolytic activity and cytotoxicity. Therefore, conjugation of Tryasine with silver nanoparticles is a promising treatment candidate for bacterial infection with low toxicity.