Exploring the Therapeutic Promise of Cationic Antibacterial Peptides

Abstract

The increasing global risk of antibiotic-resistant bacterial infections establishes the urgent need for novel and effective antimicrobial therapies. Cationic antimicrobial peptides (CAMPs) are a crucial component of the immediate, non-specific defence against infections in numerous species. Their potential as a new class of antimicrobials is encouraging, and ongoing research seeks to optimize their pharmacokinetics and pharmacodynamics, improve their stability, and address toxicity issues. This study examines the potential of CAMPs as novel antibacterial therapeutics, highlighting their unique structure and mechanism of action, which allows them to target bacterial membranes and disrupt their integrity, making them effective against a wide range of bacteria, including multidrug-resistant strains. Developing reliable and standardized evaluation assays, addressing regulatory and economic barriers, and advancing our comprehension of the interactions between CAMPs and the host immune system are future directions of research. CAMPs have the potential to become indispensable tools in the battle against bacterial infections if further research and development are conducted.

References

1. 1. Griffith, A., Mateen, A., Markowitz, K., Singer, S. R., Cugini, C., Shimizu, E & Kumar, V. (2022). Alternative antibiotics in dentistry: Antimicrobial peptides. Pharmaceutics, 14(8), 1679.
2. 2. Lin, B., Li, R., Handley, T. N., Wade, J. D., Li, W., & O’Brien-Simpson, N. M. (2021). Cationic antimicrobial peptides are leading the way to combat uropathogenic infections. ACS Infectious Diseases, 7(11), 2959-2970.
3. 3. Aisenbrey, C., Marquette, A., & Bechinger, B. (2019). The mechanisms of action of cationic antimicrobial peptides are refined by novel concepts from biophysical investigations. Antimicrobial Peptides: Basics for Clinical Application, 33-64.
4. 4. Browne, K., Chakraborty, S., Chen, R., Willcox, M. D., Black, D. S., Walsh, W. R., & Kumar, N. (2020). A new era of antibiotics: the clinical potential of antimicrobial peptides. International journal of molecular sciences, 21(19), 7047.
5. 5. Mookherjee, N., Anderson, M. A., Haagsman, H. P., & Davidson, D. J. (2020). Antimicrobial host defense peptides: functions and clinical potential. Nature reviews Drug discovery, 19(5), 311-332.
6. 6. Zhu, Y., Hao, W., Wang, X., Ouyang, J., Deng, X., Yu, H., & Wang, Y. (2022). Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug‐resistant infections. Medicinal Research Reviews, 42(4), 1377-1422.
7. 7. van der Does, A. M., Hiemstra, P. S., & Mookherjee, N. (2019). Antimicrobial host defense peptides: immunomodulatory functions and translational prospects. Antimicrobial Peptides: Basics for Clinical Application, 149-171.
8. 8. Magana, M., Pushpanathan, M., Santos, A. L., Leanse, L., Fernandez, M., Ioannidis, A & Tegos, G. P. (2020). The value of antimicrobial peptides in the age of resistance. The Lancet Infectious Diseases, 20(9), e216-e230.
9. 9. Mahlapuu, M., Björn, C., & Ekblom, J. (2020). Antimicrobial peptides as therapeutic agents: Opportunities and challenges. Critical reviews in biotechnology, 40(7), 978-992.
10. 10. Deslouches, B., Montelaro, R. C., Urish, K. L., & Di, Y. P. (2020). Engineered cationic antimicrobial peptides (eCAPs) to combat multidrug-resistant bacteria. Pharmaceutics, 12(6), 501.
11. 11. Valenti, G. E., Alfei, S., Caviglia, D., Domenicotti, C., & Marengo, B. (2022). Antimicrobial peptides and cationic nanoparticles: a broad-spectrum weapon to fight multi-drug resistance not only in bacteria. International Journal of Molecular Sciences, 23(11), 6108.
12. 12. Leon Madrazo, A., & Segura Campos, M. R. (2020). Review of antimicrobial peptides as promoters of food safety: Limitations and possibilities within the food industry. Journal of Food Safety, 40(6), e12854.
13. 13. Tornesello, A. L., Borrelli, A., Buonaguro, L., Buonaguro, F. M., & Tornesello, M. L. (2020). Antimicrobial peptides as anticancer agents: functional properties and biological activities. Molecules, 25(12), 2850.
14. 14. Seyfi, R., Kahaki, F. A., Ebrahimi, T., Montazersaheb, S., Eyvazi, S., Babaeipour, V., & Tarhriz, V. (2020). Antimicrobial peptides (AMPs): roles, functions, and mechanism of action. International Journal of Peptide Research and Therapeutics, 26, 1451-1463.
15. 15. Liu, Y., Shi, J., Tong, Z., Jia, Y., Yang, B., & Wang, Z. (2021). The revitalization of antimicrobial peptides in the resistance era. Pharmacological Research, 163, 105276.
16. 16. Yang, M., Zhang, C., Zhang, M. Z., & Zhang, S. (2018). Beta-defensin-derived cationic antimicrobial peptides with potent killing activity against gram-negative and gram-positive bacteria. BMC Microbiology, 18(1), 1-14.
17. 17. Grant, T. M., Rennison, D., Krause, A. L., Mros, S., Ferguson, S. A., Cook, G. M & Svenson, J. (2022). Stereochemical Effects on the Antimicrobial Properties of Tetrasubstituted 2, 5-Diketopiperazines. ACS Medicinal Chemistry Letters, 13(4), 632-640.
18. 18. Wang, X., Sun, Y., Wang, F., You, L., Cao, Y., Tang, R. & Cui, X. (2020). A novel endogenous antimicrobial peptide CAMP 211-225 derived from casein in human milk. Food & Function, 11(3), 2291-2298.
19. 19. Devine, D. A., & Hancock, R. E. (2002). Cationic peptides: distribution and mechanisms of resistance. Current pharmaceutical design, 8(9), 703-714.
20. 20. da Cunha, N. B., Cobacho, N. B., Viana, J. F., Lima, L. A., Sampaio, K. B., Dohms, S. S & Dias, S. C. (2017). The next generation of antimicrobial peptides (AMPs) as molecular therapeutic tools for the treatment of diseases with social and economic impacts. Drug Discovery Today, 22(2), 234-248.
21. 21. Lei, J., Sun, L., Huang, S., Zhu, C., Li, P., He, J., ... & He, Q. (2019). The antimicrobial peptides and their potential clinical applications. American journal of translational research, 11(7), 3919.
22. 22. Pervin, Z., & Hassan, M. M. (2021). Synergistic therapeutic actions of antimicrobial peptides to treat multidrug-resistant bacterial infection. Reviews and Research in Medical Microbiology, 32(2), 83-89.
23. 23. Cardoso, M. H., Meneguetti, B. T., Costa, B. O., Buccini, D. F., Oshiro, K. G., Preza, S. L & Franco, O. L. (2019). Non-lytic antibacterial peptides that translocate through bacterial membranes to act on intracellular targets. International Journal of Molecular Sciences, 20(19), 4877.
24. 24. Um, J., Manguy, J., Anes, J., Jacquier, J. C., Hurley, D., Dillon, E. T., ... & Shields, D. C. (2021). Enriching antimicrobial peptides from milk hydrolysates using pectin/alginate food-gels. Food Chemistry, 352, 129220.
25. 25. Malanovic, N., & Lohner, K. (2016). Gram-positive bacterial cell envelopes: The impact on the activity of antimicrobial peptides. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1858(5), 936-946.
26. 26. Lima, B., Ricci, M., Garro, A., Juhász, T., Szigyártó, I. C., Papp, Z. I., & Enriz, R. D. (2021). New short cationic antibacterial peptides. Synthesis, biological activity, and mechanism of action. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1863(10), 183665.
27. 27. Ageitos, J. M., Sánchez-Pérez, A., Calo-Mata, P., & Villa, T. G. (2017). Antimicrobial peptides (AMPs): Ancient compounds that represent novel weapons in the fight against bacteria. Biochemical pharmacology, 133, 117-138.
28. 28. Lee, E. Y., Lee, M. W., & Wong, G. C. (2019, April). Modulation of toll-like receptor signaling by antimicrobial peptides. In Seminars in cell & developmental biology (Vol. 88, pp. 173-184). Academic Press.
29. 29. Ramesh, S., Govender, T., Kruger, H. G., de la Torre, B. G., & Albericio, F. (2016). Short AntiMicrobial Peptides (SAMPs) as a class of extraordinarily promising therapeutic agents. Journal of Peptide Science, 22(7), 438-451.
30. 30. Kosikowska, P., & Lesner, A. (2016). Antimicrobial peptides (AMPs) as drug candidates: a patent review (2003–2015). Expert opinion on therapeutic patents, 26(6), 689-702.
31. 31. Haney, E. F., Mansour, S. C., & Hancock, R. E. (2017). Antimicrobial peptides: an introduction. Antimicrobial peptides: methods and protocols, 3-22.
32. 32. Bechinger, B., & Gorr, S. U. (2017). Antimicrobial peptides: mechanisms of action and resistance. Journal of dental research, 96(3), 254-260.
33. 33. Juárez-López, D., Morales-Ruiz, E., Herrera-Zúñiga, L. D., González-Carrera, Z., Cuevas-Reyes, E., Corzo, G., ... & Villegas, E. (2023). The Resilience of Pseudomonas aeruginosa to Antibiotics and the Designing of Antimicrobial Peptides to Overcome Microbial Resistance. Current Medicinal Chemistry, 30(1), 72-103.
34. 34. Maria-Neto, S., de Almeida, K. C., Macedo, M. L. R., & Franco, O. L. (2015). Understanding bacterial resistance to antimicrobial peptides: From the surface to deep inside. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1848(11), 3078-3088.
35. 35. Strempel, N., Strehmel, J., & Overhage, J. (2015). Potential application of antimicrobial peptides in the treatment of bacterial biofilm infections. Current pharmaceutical design, 21(1), 67-84.
36. 36. Marr, A. K., Gooderham, W. J., & Hancock, R. E. (2006). Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Current opinion in pharmacology, 6(5), 468-472.
37. 37. Solov’eva, T., Davydova, V., Krasikova, I., & Yermak, I. (2013). Marine compounds with therapeutic potential in gram-negative sepsis. Marine drugs, 11(6), 2216-2229.
38. 38. Brandenburg, K., Heinbockel, L., Correa, W., & Lohner, K. (2016). Peptides with dual mode of action: Killing bacteria and preventing endotoxin-induced sepsis. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1858(5), 971-979.
39. 39. Kościuczuk, E. M., Lisowski, P., Jarczak, J., Strzałkowska, N., Jóźwik, A., Horbańczuk, J., ... & Bagnicka, E. (2012). Cathelicidins: the family of antimicrobial peptides. A review. Molecular biology reports, 39, 10957-10970.
40. 40. Scott, M. G., & Hancock, R. E. (2000). Cationic antimicrobial peptides and their multifunctional role in the immune system. Critical Reviews™ in Immunology, 20(5). 407-31.
41. 41. Ahmed, S., Ahmed, M. Z., Rafique, S., Almasoudi, S. E., Shah, M., Jalil, N. A. C., & Ojha, S. C. (2023). Recent Approaches for Downplaying Antibiotic Resistance: Molecular Mechanisms. BioMed Research International, 2023 (1), 5250040.
42. 42. Weghuber, J., Aichinger, M. C., Brameshuber, M., Wieser, S., Ruprecht, V., Plochberger, B., & Schütz, G. J. (2011). Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells. Biochimica et Biophysica Acta (BBA)-Biomembranes,1808(10), 2581-2590.
43. 43. Teixeira, V., Feio, M. J., & Bastos, M. (2012). Role of lipids in the interaction of antimicrobial peptides with membranes. Progress in lipid research, 51(2), 149-177.
44. 44. Alfei, S., & Schito, A. M. (2020). From nanobiotechnology, positively charged biomimetic dendrimers as novel antibacterial agents: A review. Nanomaterials, 10(10), 2022.
45. 45. Barreto-Santamaría, A., Patarroyo, M. E., & Curtidor, H. (2019). Designing and optimizing new antimicrobial peptides: All targets are not the same. Critical Reviews in Clinical Laboratory Sciences, 56(6), 351-373.
46. 46. Sharma, K., Aaghaz, S., Shenmar, K., & Jain, R. (2018). Short antimicrobial peptides. Recent patents on anti-infective drug discovery, 13(1), 12-52.
47. 47. Hadley, B. E., & EW Hancock, R. (2010). Strategies for the discovery and advancement of novel cationic antimicrobial peptides. Current topics in medicinal chemistry, 10(18), 1872-1881.
48. 48. Kang, S. J., Park, S. J., Mishig-Ochir, T., & Lee, B. J. (2014). Antimicrobial peptides: therapeutic potentials. Expert review of anti-infective therapy, 12(12), 1477-1486.
49. 49. Onaizi, S. A., & Leong, S. S. (2011). Tethering antimicrobial peptides: current status and potential challenges. Biotechnology advances, 29(1), 67-74.
50. 50. Kundu, R. (2020). Cationic amphiphilic peptides: Synthetic antimicrobial agents inspired by nature. ChemMedChem, 15(20), 1887-1896.
51. 51. Guilhelmelli, F., Vilela, N., Albuquerque, P., Derengowski, L. D. S., Silva-Pereira, I., & Kyaw, C. M. (2013). Antibiotic development challenges: the various mechanisms of action of antimicrobial peptides and bacterial resistance. Frontiers in microbiology, 4, 353.
52. 52. Gera, S., Kankuri, E., & Kogermann, K. (2022). Antimicrobial peptides–unleashing their therapeutic potential using nanotechnology. Pharmacology & Therapeutics, 232, 107990.
53. 53. Lin, S., Wade, J. D., & Liu, S. (2020). De novo design of flavonoid-based mimetics of cationic antimicrobial peptides: Discovery, development, and applications. Accounts of Chemical Research, 54(1), 104-119.
54. 54. Ciumac, D., Gong, H., Hu, X., & Lu, J. R. (2019). Membrane targeting cationic antimicrobial peptides. Journal of colloid and interface science, 537, 163-185.
55. 55. Schulze, M., Dathe, M., Waberski, D., & Müller, K. (2016). Liquid storage of boar semen: Current and future perspectives on the use of cationic antimicrobial peptides to replace antibiotics in semen extenders. Theriogenology, 85(1), 39-46.
56. 56. Jafari, A., Babajani, A., Sarrami Forooshani, R., Yazdani, M., & Rezaei-Tavirani, M. (2022). Clinical applications and anticancer effects of antimicrobial peptides: From bench to bedside. Frontiers in Oncology, 12, 350.
57. 57. Wang, J., Dou, X., Song, J., Lyu, Y., Zhu, X., Xu, L & Shan, A. (2019). Antimicrobial peptides: Promising alternatives in the post-feeding antibiotic era. Medicinal research reviews, 39(3), 831-859.
58. 58. Koo, H. B., & Seo, J. (2019). Antimicrobial peptides under clinical investigation. Peptide Science, 111(5), e24122.
59. 59. Jiang, Y., Chen, Y., Song, Z., Tan, Z., & Cheng, J. (2021). Recent advances in the design of antimicrobial peptides and polypeptides toward clinical translation. Advanced Drug Delivery Reviews, 170, 261-280.
60. 60. Giuliani, A., & Rinaldi, A. C. (2011). Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cellular and Molecular Life Sciences, 68, 2255-2266.
61. 61. Gan, B. H., Gaynord, J., Rowe, S. M., Deingruber, T., & Spring, D. R. (2021). The multifaceted nature of antimicrobial peptides: Current synthetic chemistry approaches and future directions. Chemical Society Reviews, 50(13), 7820-7880.
62. 62. Kalelkar, P. P., Riddick, M., & García, A. J. (2022). Biomaterial-based antimicrobial therapies for the treatment of bacterial infections. Nature Reviews Materials, 7(1), 39-54.
63. 63. Wang, L., Qu, L., Lin, S., Yang, Q., Zhang, X., Jin, L & Sun, D. (2022). Biological Functions and Applications of Antimicrobial Peptides. Current Protein and Peptide Science, 23(4), 226-247.
64. 64. Mohammed, I., Said, D. G., & Dua, H. S. (2017). Human antimicrobial peptides in ocular surface defense. Progress in retinal and eye research, 61, 1-22.