Список литературы

2658-6533

Research Results in Biomedicine

2658-6533

10.18413/2658-6533-2025-11-4-0-6

3941

Pharmacology

Development of Novel Antimicrobial Peptides Targeting Antibiotic-Resistant Pseudomonas aeruginosa

Salama

Ali H.

Salama

Ali H.

asalama@meu.edu.jo

2025

11400

Background: Antibiotic resistance is a global health threat, especially with pathogens like Pseudomonas aeruginosa, which displays high resistance to many antibiotics. Innovative solutions, such as antimicrobial peptides (AMPs), are being explored to combat these multidrug-resistant organisms. The aim of the study: This study aimed to design and synthesize an antimicrobial peptide (AMP) effective against both antibiotic-resistant and susceptible strains of P. aeruginosa, while ensuring safety for human cells. Materials and methods: A novel antimicrobial peptide, WW-185, was designed based on the structure-function relationship of existing AMPs. Its antimicrobial activity was evaluated through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays against standard and multidrug-resistant P. aeruginosa strains. Hemolytic activity was tested to assess safety for human erythrocytes, and time-kill assays were performed to study the peptide’s bactericidal action. Results: WW-185 demonstrated potent antimicrobial activity, with MIC and MBC values comparable to conventional antibiotics. It showed low hemolytic effects on human erythrocytes and exhibited rapid bactericidal action, killing bacteria within 15 minutes and maintaining efficacy for up to 24 hours. The peptide’s activity was attributed to bacterial membrane disruption, facilitated by its structural features. Conclusion: WW-185 is a promising antimicrobial candidate, with potent efficacy against multidrug-resistant P. aeruginosa and low toxicity to human cells. Its potential to reduce rapid resistance development makes it a valuable option for treating antibiotic-resistant infections

bactericidal activityminimum inhibitory concentrationminimum bactericidal concentrationmembrane permeabilizationhemolytic activityWW-185 peptide

Список литературы

Lyu Z, Yang P, Lei J, et al. Biological function of antimicrobial peptides on suppressing pathogens and improving host immunity. Antibiotics. 2023;12(6):1037.&rlm; DOI: https://doi.org/10.3390/antibiotics12061037

King AM, Zhang Z, Glassey E, et al. Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra. Nature Microbiology. 2023;8(12):2420-2434.&rlm; DOI: https://doi.org/10.1038/s41564-023-01524-6

Chen N, Jiang C. Antimicrobial peptides: Structure, mechanism, and modification. European Journal of Medicinal Chemistry. 2023;255:115377.&rlm; DOI: https://doi.org/10.1016/j.ejmech.2023.115377

Chen X, Su S, Yan Y, et al. Anti-Pseudomonas aeruginosa activity of natural antimicrobial peptides when used alone or in combination with antibiotics. Frontiers in Microbiology. 2023;14:1239540.&rlm; DOI: https://doi.org/10.3389/fmicb.2023.1239540

Juárez-López D, Morales-Ruiz E, Herrera-Zúñiga LD, et al. The resilience of Pseudomonas aeruginosa to antibiotics and the designing of antimicrobial peptides to overcome microbial resistance. Current Medicinal Chemistry. 2023;30(1):72-103.&rlm; DOI: https://doi.org/10.2174/0929867329666220907100505

Klimovich A, Bosch TCG. Novel technologies uncover novel ‘anti’-microbial peptides in hydra shaping the species-specific microbiome. Philosophical Transactions of the Royal Society B: Biological Sciences. 2024;379(1901):58. DOI: https://doi.org/10.1098/rstb.2023.0058

Zhang W, An Z, Bai Y, et al. A novel antimicrobial peptide Scyreptin1-30 from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model. Biochemical Pharmacology. 2023;218:115917.&rlm; DOI: https://doi.org/10.1016/j.bcp.2023.115917

Mildenberger V, Alpízar-Pedraza D, Martell-Huguet EM, et al. The Designed Pore-Forming Antimicrobial Peptide C14R Combines Excellent Activity against the Major Opportunistic Human Pathogen Pseudomonas aeruginosa with Low Cytotoxicity. Pharmaceuticals. 2024;17(1):83. &rlm;DOI: https://doi.org/10.3390/ph17010083

Jing R, Zhang L, Li R, et al. Milk‐derived extracellular vesicles functionalized with anti‐tumour necrosis factor‐α nanobody and anti‐microbial peptide alleviate ulcerative colitis in mice. Journal of Extracellular Vesicles. 2024;13(6):e12462. DOI: https://doi.org/10.1002/jev2.12462

Hyun JE, Hwang CY. Antimicrobial Peptide Reduces Cytotoxicity and Inflammation in Canine Epidermal Keratinocyte Progenitor Cells Induced by Pseudomonas aeruginosa Infection. Veterinary Sciences. 2024;11(6):235.&rlm; DOI: https://doi.org/10.3390/vetsci11060235

Ji S, An F, Zhang T, et al. Antimicrobial peptides: An alternative to traditional antibiotics. European Journal of Medicinal Chemistry. 2024;265:116072. DOI: https://doi.org/10.1016/j.ejmech.2023.116072

Jordan O, Gan BH, Alwan S, et al. Highly Potent Cationic Chitosan Derivatives Coupled to Antimicrobial Peptide Dendrimers to Combat Pseudomonas aeruginosa. Advanced Healthcare Materials. 2024;13(19):2304118. DOI: https://doi.org/10.1002/adhm.202304118

Murphy RA, Pizzato J, Cuthbertson L, et al. Antimicrobial peptide glatiramer acetate targets Pseudomonas aeruginosa lipopolysaccharides to breach membranes without altering lipopolysaccharide modification. npj Antimicrobials and Resistance. 2024;2(1):4.&rlm; DOI: https://doi.org/10.1038/s44259-024-00022-x

He S, Deber CM. Interaction of designed cationic antimicrobial peptides with the outer membrane of gram-negative bacteria. Scientific Reports. 2024;14(1):1894.&rlm; DOI: https://doi.org/10.1038/s41598-024-51716-1

Roque-Borda CA, Primo LMDG, Franzyk H, et al. Recent advances in the development of antimicrobial peptides against ESKAPE pathogens. Heliyon. 2024;10(11):e31958. DOI: https://doi.org/10.1016/j.heliyon.2024.e31958

Wan X, Wang W, Zhu J, et al. Antibacterial peptide Reg4 ameliorates Pseudomonas aeruginosa-induced pulmonary inflammation and fibrosis. Microbiology Spectrum. 2024;12(5):e03905-23.&rlm; DOI: https://doi.org/10.1128/spectrum.03905-23&rlm;

Büyükkiraz ME, Kesmen Z. Antimicrobial peptides (AMPS): A promising class of antimicrobial compounds. Journal of Applied Microbiology. 2022;132(3):1573-1596. DOI: https://doi.org/10.1111/jam.15314

Li Z, Qu W, Zhang D, et al. The antimicrobial peptide chensinin-1b alleviates the inflammatory response by targeting the TLR4/NF-κB signaling pathway and inhibits Pseudomonas aeruginosa infection and LPS-mediated sepsis. Biomedicine and Pharmacotherapy. 2023;165:115227.&rlm; DOI: https://doi.org/10.1016/j.biopha.2023.115227

Talapko J, Me&scaron;trović T, Juzba&scaron;ić M, et al. Antimicrobial peptides—mechanisms of action, antimicrobial effects and clinical applications. Antibiotics. 2022;11(10):1417. DOI: https://doi.org/10.3390/antibiotics11101417

Bucataru C, Ciobanasu C. Antimicrobial peptides: Opportunities and challenges in overcoming resistance. Microbiological Research. 2024;286:127822. DOI: https://doi.org/10.1016/j.micres.2024.127822

Li G, Lai Z, Shan A. Advances of antimicrobial peptide‐based biomaterials for the treatment of bacterial infections. Advanced Science. 2023;10(11):2206602.&rlm; DOI: https://doi.org/10.1002/advs.202206602

Cresti L, Cappello G, Pini A. Antimicrobial peptides towards clinical application—a long history to be concluded. International Journal of Molecular Sciences. 2024;25(9):4870. DOI: https://doi.org/10.3390/ijms25094870

&rlm;23. Fahmy L, Ali YM, Seilly D, et al. An attacin antimicrobial peptide, Hill_BB_C10074, from Hermetia illucens with anti-Pseudomonas aeruginosa activity. BMC Microbiology. 2023;23(1):378.&rlm; DOI: https://doi.org/10.1186/s12866-023-03131-1

Wood S J, Kuzel TM, Shafikhani SH. Pseudomonas aeruginosa: infections, animal modeling, and therapeutics. Cells. 2023;12(1):199.&rlm; DOI: https://doi.org/10.3390/cells12010199

Maasch JRMA, Torres MDT, Melo MCR, et al. Molecular De-Extinction of Ancient Antimicrobial Peptides Enabled by Machine Learning. 2022;11(15):516443. DOI: https://doi.org/10.1101/2022.11.15.516443

Sathe N, Beech P, Croft L, et al. Pseudomonas aeruginosa: Infections and novel approaches to treatment “Knowing the enemy” the threat of Pseudomonas aeruginosa and exploring novel approaches to treatment. Infectious Medicine. 2023;2(3):178-194.&rlm; DOI: https://doi.org/10.1016/j.imj.2023.05.003

Sanya DRA, Onésime D, Vizzarro G, et al. Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections. BMC Microbiology. 2023;23(1):86.&rlm; DOI: https://doi.org/10.1186/s12866-023-02832-x

Johnson K, Delaney JC, Guillard T, et al. Development of an antibody fused with an antimicrobial peptide targeting Pseudomonas aeruginosa: A new approach to prevent and treat bacterial infections. PLoS Pathogens. 2023;19(9):e1011612.&rlm; DOI: https://doi.org/10.1371/journal.ppat.1011612