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Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers

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Abstract

Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL), an AMP mimics, has gained attention due to its broad-spectrum antibacterial activities, but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid, e.g., alanine (A), tryptophan (W) or phenylalanine (F), to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The G. mellonella infection model demonstrates that the copolymers are effective against the S. aureus infection in vivo. The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.

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References

  1. Hutchings, M. I.; Truman, A. W.; Wilkinson, B. Antibiotics: past, present and future. Curr. Opin. Microbiol. 2019, 51, 72–80.

    Article  CAS  PubMed  Google Scholar 

  2. Broughton, C. E.; Van Den Berg, H. A.; Wemyss, A. M.; Roper, D. I.; Rodger, A. Beyond the discovery void: new targets for antibacterial compounds. Sci. Prog. 2016, 99, 153–182.

    Article  PubMed  Google Scholar 

  3. Shen, S.; Huang, Y.; Yuan, A.; Lv, F.; Liu, L.; Wang, S. Electrochemical regulation of antibacterial activity using ferrocene-containing antibiotics. CCS Chem. 2021, 3, 129–135.

    Article  CAS  Google Scholar 

  4. Duval, R. E.; Grare, M.; Demore, B. Fight against antimicrobial resistance: we always need new antibacterials but for right bacteria. Molecules 2019, 24, 9.

    Article  Google Scholar 

  5. Blaskovich, M. A. T. The fight against antimicrobial resistance is confounded by a global increase in antibiotic usage. ACS Infect. Dis. 2018, 4, 868–870.

    Article  CAS  PubMed  Google Scholar 

  6. Luong, H. X.; Thanh, T. T.; Tran, T. H. Antimicrobial peptides-advances in development of therapeutic applications. Life Sci. 2020, 260, 118407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Xie, X.; Gao, B.; Ma, Z.; Liu, J.; Zhang, J.; Liang, J.; Chen, Z.; Wu, L.; Li, W. Host-guest interaction driven peptide assembly into photoresponsive two-dimensional nanosheets with switchable antibacterial activity. CCS Chem. 2021, 3, 1949–1962.

    Article  CAS  Google Scholar 

  8. Cruz, J.; Ortiz, C.; Guzman, F.; Fernandez-Lafuente, R.; Torres, R. Antimicrobial peptides: promising compounds against pathogenic microorganisms. Curr. Med. Chem. 2014, 21, 2299–2321.

    Article  CAS  PubMed  Google Scholar 

  9. Hancock, R. E. W.; Sahl, H. G. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 2006, 24, 1551–1557.

    Article  CAS  PubMed  Google Scholar 

  10. Da Costa, J. P.; Cova, M.; Ferreira, R.; Vitorino, R. Antimicrobial peptides: an alternative for innovative medicines. Appl. Microbiol. Biot. 2015, 99, 2023–2040.

    Article  Google Scholar 

  11. Wang, J. J.; Dou, X. J.; Song, J.; Lyu, Y. F.; Zhu, X.; Xu, L.; Li, W. Z.; Shan, A. S. Antimicrobial peptides: promising alternatives in the post feeding antibiotic era. Med. Res. Rev. 2019, 39, 831–859.

    Article  CAS  PubMed  Google Scholar 

  12. Kawano, Y.; Jordan, O.; Hanawa, T.; Borchard, G.; Patrulea, V. Are antimicrobial peptide dendrimers an Escape from ESKAPE. Adv. Wound Care 2020, 9, 378–395.

    Article  Google Scholar 

  13. Ciornei, C. D.; Sigurdardottir, T.; Schmidtchen, A.; Bodelsson, M. Antimicrobial and chemoattractant activity, lipopolysaccharide neutralization, cytotoxicity, and inhibition by serum of analogs of human cathelicidin LL-37. Antimicrob. Agents Chemother. 2005, 49, 2845–2850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hartlieb, M.; Williams, E. G. L.; Kuroki, A.; Perrier, S.; Locock, K. E. S. Antimicrobial polymers: mimicking amino acid functionality, sequence control and three-dimensional structure of host-defense peptides. Curr. Med. Chem. 2017, 24, 2115–2140.

    Article  CAS  PubMed  Google Scholar 

  15. Salas-Ambrosio, P.; Tronnet, A.; Verhaeghe, P.; Bonduelle, C. Synthetic polypeptide polymers as simplified analogues of antimicrobial peptides. Biomacromolecules 2021, 22, 57–75.

    Article  CAS  PubMed  Google Scholar 

  16. Shen, W.; He, P.; Xiao, C.; Chen, X. From antimicrobial peptides to antimicrobial poly(alpha-amino acid)s. Adv. Healthc. Mater. 2018, 7, 1800354.

    Article  Google Scholar 

  17. Shima, S.; Matsuoka, H.; Iwamoto, T.; Sakai, H. Antibacterial action of epsilon-poly-L-lysine. J. Antibiot. 1984, 37, 1449–1455.

    Article  CAS  Google Scholar 

  18. Katchalski, E.; Grossfeld, I.; Frankel, M. Poly-condensation of alpha-amino acid derivatives. 3. Poly-lysine. J. Am. Chem. Soc. 1948, 70, 2094–2101.

    Article  CAS  PubMed  Google Scholar 

  19. Katchalski, E.; Bichowskislomnitzki, L.; Volcani, B. E. The action of some water-soluble poly-alpha-amino acids on bacteria. Biochem. J. 1953, 55, 671–680.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mayandi, V.; Xi, Q. X.; Goh, E. T. L.; Koh, S. K.; Toh, T. Y. J.; Barathi, V. A.; Fazil, M.; Chalasani, M. L. S.; Varadarajan, J.; Ting, D. S. J.; Beuerman, R. W.; Chan, L. W.; Agrawal, R.; Barkham, T. M. S.; Zhou, L.; Verma, N. K.; Lakshminarayanan, R. Rational substitution of epsilon-lysine for alpha-lysine enhances the cell and membrane selectivity of pore-forming melittin. J. Med. Chem. 2020, 63, 3522–3537.

    Article  CAS  PubMed  Google Scholar 

  21. Zhou, C. C.; Qi, X. B.; Li, P.; Chen, W. N.; Mouad, L.; Chang, M. W.; Leong, S. S. J.; Chan-Park, M. B. High potency and broad-spectrum antimicrobial peptides synthesized via ring-opening polymerization of alpha-aminoacid-N-carboxyanhydrides. Biomacromolecules 2010, 11, 60–67.

    Article  CAS  PubMed  Google Scholar 

  22. Zhou, X.; Su, X.; Tan, Z.; Zhou, C. Synthesis of triblock amphiphilic copolypeptides with excellent antibacterial activity. Eur. Polym. J. 2018, 106, 175–181.

    Article  CAS  Google Scholar 

  23. Lam, S. J.; O’Brien-Simpson, N. M.; Pantarat, N.; Sulistio, A.; Wong, E. H.; Chen, Y. Y.; Lenzo, J. C.; Holden, J. A.; Blencowe, A.; Reynolds, E. C.; Qiao, G. G. Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nat. Microbiol. 2016, 1, 16162.

    Article  CAS  PubMed  Google Scholar 

  24. Chen, Y. F.; Lai, Y. D.; Chang, C. H.; Tsai, Y. C.; Tang, C. C.; Jan, J. S. Star-shaped polypeptides exhibit potent antibacterial activities. Nanoscale 2019, 11, 11696–11708.

    Article  CAS  PubMed  Google Scholar 

  25. Chen, S. J.; Huang, S. T.; Li, Y.; Zhou, C. C. Recent advances in epsilon-poly-L-lysine and L-lysine-based dendrimer synthesis, modification, and biomedical applications. Front. Chem. 2021, 9, 14.

    Article  CAS  Google Scholar 

  26. Hyldgaard, M.; Mygind, T.; Vad, B. S.; Stenvang, M.; Otzen, D. E.; Meyer, R. L. The antimicrobial mechanism of action of epsilon-poly-L-lysine. Appl. Environ. Microbiol. 2014, 80, 7758–7770.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Zou, Y. J.; He, S. S.; Du, J. Z. Epsilon-poly(L-lysine)-based hydrogels with fast-acting and prolonged antibacterial activities. Chinese J. Polym. Sci. 2018, 36, 1239–1250.

    Article  CAS  Google Scholar 

  28. Shi, C.; He, Y.; Feng, X. B.; Fu, D. H. Epsilon-polylysine and next-generation dendrigraft poly-L-lysine: chemistry, activity, and applications in biopharmaceuticals. J. Biomater. Sci., Polym. Ed. 2015, 26, 1343–1356.

    Article  CAS  PubMed  Google Scholar 

  29. Liu, X.; Guo, J. W.; Liu, Y. D.; Liu, M.; Liu, H.; Han, M. M.; Ji, S. X. Antibacterial thermoplastic polyurethane/PL-DOSS composite films. Chinese J. Polym. Sci. 2021, 39, 1020–1028.

    Article  CAS  Google Scholar 

  30. Ye, R.; Xu, H.; Wan, C.; Peng, S.; Wang, L.; Xu, H.; Aguilar, Z. P.; Xiong, Y.; Zeng, Z.; Wei, H. Antibacterial activity and mechanism of action of ε-poly-L-lysine. Biochem. Biophys. Res. Commun. 2013, 439, 148–153.

    Article  CAS  PubMed  Google Scholar 

  31. Shukla, S. C.; Singh, A.; Pandey, A. K.; Mishra, A. Review on production and medical applications of ε-polylysine. Biochem. Eng. J. 2012, 65, 70–81.

    Article  CAS  Google Scholar 

  32. Harada, K. Thermal homopolymerization of lysine and copolymerization with neutral and acidic amino acids. Bull. Chem. Soc. Jpn. 1959, 32, 1007–1008.

    Article  CAS  Google Scholar 

  33. Harada K; W., F. S. Characterization of thermal polymers of neutral α-amino acids with dicarboxylic amino acids or lysine. Arch. Biochem. Biophys. 1965, 109, 49–56.

    Article  CAS  PubMed  Google Scholar 

  34. Scholl, M.; Kadlecova, Z.; Klok, H. A. Dendritic and hyperbranched polyamides. Prog. Polym. Sci. 2009, 34, 24–61.

    Article  CAS  Google Scholar 

  35. Liu, X.; Yang, Y.; Han, M.; Guo, J.; Liu, H.; Liu, Y.; Xu, J.; Ji, S.; Chen, X. Guanylated hyperbranched polylysines with high in vitro and in vivo antifungal activity. Adv. Healthc. Mater. 2022, 2201091.

  36. Kadlecova, Z.; Rajendra, Y.; Matasci, M.; Baldi, L.; Hacker, D. L.; Wurm, F. M.; Klok, H. A. DNA delivery with hyperbranched polylysine: a comparative study with linear and dendritic polylysine. J. Controlled Release 2013, 169, 276–288.

    Article  CAS  Google Scholar 

  37. Kadlecova, Z.; Baldi, L.; Hacker, D.; Wurm, F. M.; Klok, H. A. Comparative study on the in vitro cytotoxicity of linear, dendritic, and hyperbranched polylysine analogues. Biomacromolecules 2012, 13, 3127–3137.

    Article  CAS  PubMed  Google Scholar 

  38. Thompson, M.; Scholz, C. Highly branched polymers based on poly(amino acid)s for biomedical application. Nanomaterials 2021, 11, 23.

    Article  Google Scholar 

  39. Ramarao, N.; Nielsen-Leroux, C.; Lereclus, D. The insect Galleria mellonella as a powerful infection model to investigate bacterial pathogenesis. JoVE 2012, 70, 4392.

    Google Scholar 

  40. Balouiri, M.; Sadiki, M.; Ibnsouda, S. K. Methods for in vitro evaluating antimicrobial activity: a review. J. Pharm. Anal. 2016, 6, 71–79.

    Article  PubMed  Google Scholar 

  41. Fischer, W. Lipoteichoic acid and lipids in the membrane of Staphylococcus aureus. Med. Microbiol. Immunol. 1994, 183, 61–76.

    Article  CAS  PubMed  Google Scholar 

  42. Beveridge, T. J. Structures of gram-negative cell walls and their derived membrane vesicles. J. Bacteriol. 1999, 181, 4725–4733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li, P.; Zhou, C.; Rayatpisheh, S.; Ye, K.; Poon, Y. F.; Hammond, P. T.; Duan, H.; Chan-Park, M. B. Cationic peptidopolysaccharides show excellent broad-spectrum antimicrobial activities and high selectivity. Adv. Mater. 2012, 24, 4130–4137.

    Article  CAS  PubMed  Google Scholar 

  44. Lu, C.; Quan, G. L.; Su, M.; Nimmagadda, A.; Chen, W. D.; Pan, M.; Teng, P.; Yu, F. Y.; Liu, X.; Jiang, L.; Du, W. Y.; Hu, W.; Yao, F.; Pan, X.; Wu, C. B.; Liu, D. J.; Cai, J. F. Molecular architecture and charging effects enhance the in vitro and in vivo performance of multi-arm antimicrobial agents based on star-shaped poly(L-lysine). Adv. Ther. 2019, 2, 11.

    Google Scholar 

  45. Yeaman, M. R.; Yount, N. Y. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev. 2003, 55, 27–55.

    Article  CAS  PubMed  Google Scholar 

  46. Nam, S. Y.; Lee, J.; Shin, S. S.; Yoo, H. J.; Yun, M.; Kim, S.; Kim, J. H.; Lee, J. H. Antibacterial and cytotoxic properties of star-shaped quaternary ammonium-functionalized polymers with different pendant groups. Polym. Chem. 2022, 13, 1763–1773.

    Article  CAS  Google Scholar 

  47. Al-Badri, Z. M.; Som, A.; Lyon, S.; Nelson, C. F.; Nusslein, K.; Tew, G. N. Investigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers. Biomacromolecules 2008, 9, 2805–2810.

    Article  CAS  PubMed  Google Scholar 

  48. Palermo, E. F.; Kuroda, K. Structural determinants of antimicrobial activity in polymers which mimic host defense peptides. Appl. Microbiol. Biot. 2010, 87, 1605–1615.

    Article  CAS  Google Scholar 

  49. Li, P.; Poon, Y. F.; Li, W.; Zhu, H.-Y.; Yeap, S. H.; Cao, Y.; Qi, X.; Zhou, C.; Lamrani, M.; Beuerman, R. W.; Kang, E.-T.; Mu, Y.; Li, C. M.; Chang, M. W.; Jan Leong, S. S.; Chan-Park, M. B. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nat. Mater. 2011, 10, 149–156.

    Article  CAS  PubMed  Google Scholar 

  50. Eisenberg, D.; Weiss, R. M.; Terwilliger, T. C.; Wilcox, W. Hydrophobic moments and protein-structure. Faraday Symp. Chem. Soc. 1982, 17, 109–120.

    Article  Google Scholar 

  51. Van den Bergen, G.; Stroet, M.; Caron, B.; Poger, D.; Mark, A. E. Curved or linear? Predicting the 3-dimensional structure of α-helical antimicrobial peptides in an amphipathic environment. FEBS Lett. 2020, 594, 1062–1080.

    Article  CAS  PubMed  Google Scholar 

  52. Su, X.; Zhou, X.; Tan, Z.; Zhou, C. Highly efficient antibacterial diblock copolypeptides based on lysine and phenylalanine. Biopolymers 2017, 107, 23041.

    Article  Google Scholar 

  53. Ramamourthy, G.; Park, J.; Seo, C.; Vogel, H. J.; Park, Y. Antifungal and antibiofilm activities and the mechanism of action of repeating lysine-tryptophan peptides against Candida albicans. Microorganisms 2020, 8, 22.

    Article  Google Scholar 

  54. Kuroda, K.; Caputo, G. A.; DeGrado, W. F. The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives. Chem. Eur. J. 2009, 15, 1123–1133.

    Article  CAS  PubMed  Google Scholar 

  55. Zasloff, M. Antimicrobial peptides of multicellular organisms. Nature 2002, 415, 389–395.

    Article  CAS  PubMed  Google Scholar 

  56. Lienkamp, K.; Madkour, A. E.; Kumar, K. N.; Nüsslein, K.; Tew, G. N. Antimicrobial polymers prepared by ring-opening metathesis polymerization: manipulating antimicrobial properties by organic counterion and charge density variation. Chem. Eur. J. 2009, 15, 11715–11722.

    Article  CAS  PubMed  Google Scholar 

  57. Chen, L. C.; Kung, S. K.; Chen, H. H.; Lin, S. B. Evaluation of zeta potential difference as an indicator for antibacterial strength of low molecular weight chitosan. Carbohydr. Polym. 2010, 82, 913–919.

    Article  CAS  Google Scholar 

  58. Henkelman, S.; Rakhorst, G.; Blanton, J.; van Oeveren, W. Standardization of incubation conditions for hemolysis testing of biomaterials. Mater. Sci. Eng., C 2009, 29, 1650–1654.

    Article  CAS  Google Scholar 

  59. Ong, Z. Y. I.; Yang, C.; Cheng, W.; Voo, Z. X.; Chin, W.; Hedrick, J. L.; Yang, Y. Y. Biodegradable cationic poly(carbonates): effect of varying side chain hydrophobicity on key aspects of gene transfection. Acta Biomater. 2017, 54, 201–211.

    Article  CAS  PubMed  Google Scholar 

  60. Chen, J.; Jiao, Z. X.; Lin, L.; Guo, Z. P.; Xu, C. N.; Li, Y. H.; Tian, H. Y.; Chen, X. S. Polylysine-modified polyethylenimines as siRNA carriers for effective tumor treatment. Chinese J. Polym. Sci. 2015, 33, 830–837.

    Article  CAS  Google Scholar 

  61. Monnery, B. D.; Wright, M.; Cavill, R.; Hoogenboom, R.; Shaunak, S.; Steinke, J. H. G.; Thanou, M. Cytotoxicity of polycations: relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity. Int. J. Pharm. 2017, 521, 249–258.

    Article  CAS  PubMed  Google Scholar 

  62. Huang, M.; Khor, E.; Lim, L. Y. Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm. Res. 2004, 21, 344–353.

    Article  CAS  PubMed  Google Scholar 

  63. Colomer, A.; Pinazo, A.; Garcia, M. T.; Mitjans, M.; Vinardell, M. P.; Infante, M. R.; Martinez, V.; Perez, L. pH-sensitive surfactants from lysine: assessment of their cytotoxicity and environmental behavior. Langmuir 2012, 28, 5900–5912.

    Article  CAS  PubMed  Google Scholar 

  64. Uppu, D.; Samaddar, S.; Hoque, J.; Konai, M. M.; Krishnamoorthy, P.; Shome, B. R.; Haldar, J. Side chain degradable cationic-amphiphilic polymers with tunable hydrophobicity show in vivo activity. Biomacromolecules 2016, 17, 3094–3102.

    Article  CAS  PubMed  Google Scholar 

  65. Choksakulnimitr, S.; Masuda, S.; Tokuda, H.; Takakura, Y.; Hashida, M. In vitro cytotoxicity of macromolecules in different cell culture systems. J. Controlled Release 1995, 34, 233–241.

    Article  CAS  Google Scholar 

  66. Morgan, D. M.; Clover, J.; Pearson, J. D. Effects of synthetic polycations on leucine incorporation, lactate dehydrogenase release, and morphology of human umbilical vein endothelial cells. J. Cell Sci. 1988, 91, 231–238.

    Article  CAS  PubMed  Google Scholar 

  67. Morgan, D. M.; Larvin, V. L.; Pearson, J. D. Biochamical characterisation of polycation-induced cytotoxicity to human vascular endothelial cells. J. Cell Sci. 1989, 94, 553–559.

    Article  CAS  PubMed  Google Scholar 

  68. Frederiksen, N.; Hansen, P. R.; Zabicka, D.; Tomczak, M.; Urbas, M.; Domraceva, I.; Björkling, F.; Franzyk, H. Alternating cationic-hydrophobic peptide/peptoid hybrids: influence of hydrophobicity on antibacterial activity and cell selectivity. ChemMedChem 2020, 15, 2544–2561.

    Article  CAS  PubMed  Google Scholar 

  69. Lee, J.; Kang, D.; Choi, J.; Huang, W.; Wadman, M.; Barron, A. E.; Seo, J. Effect of side chain hydrophobicity and cationic charge on antimicrobial activity and cytotoxicity of helical peptoids. Bioorg. Med. Chem. Lett. 2018, 28, 170–173.

    Article  CAS  PubMed  Google Scholar 

  70. Lienkamp, K.; Kumar, K. N.; Som, A.; Nüsslein, K.; Tew, G. N. “Doubly selective” antimicrobial polymers: how do they differentiate between bacteria. Chem. Eur. J. 2009, 15, 11710–11714.

    Article  CAS  PubMed  Google Scholar 

  71. Konaté, K.; Mavoungou, J. F.; Lepengué, A. N.; Aworet-Samseny, R. R. R.; Hilou, A.; Souza, A.; Dicko, M. H.; M’Batchi, B. Antibacterial activity against β-lactamase producing Methicillin and Ampicillin-resistants Staphylococcus aureus: fractional Inhibitory Concentration Index (FICI) determination. Ann. Clin. Microbiol. Antimicrob. 2012, 11, 18.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kavanagh, K.; Reeves, E. P. Exploiting the potential of insects for in vivo pathogenicity testing of microbial pathogens. FEMS Microbiol. Rev. 2004, 28, 101–112.

    Article  CAS  PubMed  Google Scholar 

  73. Desbois, A. P.; Coote, P. J. Wax moth larva (Galleria mellonella): an in vivo model for assessing the efficacy of antistaphylococcal agents. J. Antimicrob. Chemother. 2011, 66, 1785–1790.

    Article  CAS  PubMed  Google Scholar 

  74. Gibreel, T. M.; Upton, M. Synthetic epidermicin NI01 can protect Galleria mellonella larvae from infection with Staphylococcus aureus. J. Antimicrob. Chemother. 2013, 68, 2269–2273.

    CAS  PubMed  Google Scholar 

  75. Brackman, G.; Cos, P.; Maes, L.; Nelis, H. J.; Coenye, T. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrob. Agents Chemother. 2011, 55, 2655–2661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Peleg, A. Y.; Monga, D.; Pillai, S.; Mylonakis, E.; Moellering, R. C.; Eliopoulos, G. M. Reduced susceptibility to vancomycin influences pathogenicity in Staphylococcus aureus infection. J. Infect. Dis. 2009, 199, 532–536.

    Article  PubMed  Google Scholar 

  77. Gao, W.; Chua, K.; Davies, J. K.; Newton, H. J.; Seemann, T.; Harrison, P. F.; Holmes, N. E.; Rhee, H. W.; Hong, J. I.; Hartland, E. L.; Stinear, T. P.; Howden, B. P. Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent Infection. PLoS Pathog. 2010, 6, 100094.

    Article  Google Scholar 

  78. Peleg, A. Y.; Jara, S.; Monga, D.; Eliopoulos, G. M.; Moellering, R. C., Jr.; Mylonakis, E. Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics. Antimicrob. Agents Chemother. 2009, 53, 2605–2609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Tsai, C. J. Y.; Loh, J. M. S.; Proft, T. Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing. Virulence 2016, 7, 214–229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhang, X. X.; Yang, L.; Lu, X. Q.; Lv, Y.; Jiang, D.; Yu, Y.; Peng, Z.; Dong, Z. H. Characterization and property of dual-functional Zn-incorporated TiO2 micro-arc oxidation coatings: the influence of current density. J. Alloys Compd. 2019, 810, 151893.

    Article  CAS  Google Scholar 

  81. Ren, L.; Chen, J. X.; Lu, Q.; Wang, C. B.; Han, J.; Huang, K.; Pan, X. N.; Wu, H. Construction of high selectivity and antifouling nanofiltration membrane via incorporating macrocyclic molecules into active layer. J. Membr. Sci. 2020, 597, 117641.

    Article  CAS  Google Scholar 

  82. Brogden, K. A. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria. Nat. Rev. Microbiol. 2005, 3, 238–250.

    Article  CAS  PubMed  Google Scholar 

  83. Takahashi, D.; Shukla, S. K.; Prakash, O.; Zhang, G. Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity. Biochimie 2010, 92, 1236–1241.

    Article  CAS  PubMed  Google Scholar 

  84. Ganewatta, M. S.; Tang, C. Controlling macromolecular structures towards effective antimicrobial polymers. Polymer 2015, 63, A1–A29.

    Article  CAS  Google Scholar 

  85. Bechinger, B.; Gorr, S. U. Antimicrobial peptides: mechanisms of action and resistance. J. Dent. Res. 2017, 96, 254–260.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 51973212) and Department of Science and Technology of Jilin Province (No. 20210203119SF and 20210203173SF).

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  1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Hui Liu, Xiao Liu, Yuan-Qiao Cao, Ming Liu, Miao-Miao Han & Sheng-Xiang Ji

  2. University of Science and Technology of China, Hefei, 230026, China

    Hui Liu, Yuan-Qiao Cao & Sheng-Xiang Ji

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  1. Hui Liu
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Liu, H., Liu, X., Cao, YQ. et al. Engineering Antibacterial Activities and Biocompatibility of Hyperbranched Lysine-based Random Copolymers. Chin J Polym Sci 41, 345–355 (2023). https://doi.org/10.1007/s10118-022-2859-1

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