Skip to main content
Log in

Biofilm Disruption Utilizing α/β Chimeric Polypeptide Molecular Brushes

  • Article
  • Published:
Chinese Journal of Polymer Science Aims and scope Submit manuscript

Abstract

Gram-negative bacteria can cause serious infections and are well known problems in biomedical practices. Biofilms of gram-negative bacteria are notorious for their frequently encountered resistance toward antibiotics. We demonstrate that α/β chimeric polypeptide molecular brush (α/β CPMB) exerts potent activities against antibiotic-resistant gram-negative bacteria. MTT viability assay, bacterial colony counting, and live/dead staining all indicate that α/β CPMB not only inhibits biofilm formation of gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, but also effectively disrupts mature biofilms that are highly resistant to one of the most active antibiotics—colistin. The superior antibacterial performance of the α/β CPMB implies its potential topical applications in treating biofilms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Parsek, M. R.; Singh, P. K. Bacterial biofilms: An emerging link to disease pathogenesis. Annu. Rev. Microbiol. 2003, 57, 677–701.

    Article  CAS  Google Scholar 

  2. Drescher, K.; Dunkeld, J.; Nadella, C. D.; Teeffelen, S. V.; Grnjaa, I.; Wingreenb, N. S.; Stone, H. A.; Bassler, B. L. Architectural transitions in Vibrio cholerae biofilms at single-cell resolution. Proc. Natl. Acad. Sci. 2016, 113, 2066–2072.

    Article  Google Scholar 

  3. Zheng, C. X.; Zhao, Y.; Liu, Y. Recent advances in self-assembled nano-therapeutics. Chinese J. Polym. Sci. 2018, 36, 322–346.

    Article  CAS  Google Scholar 

  4. Wei, T.; Yu, Q.; Chen, H. Responsive and synergistic antibacterial coatings: Fighting against bacteria in a smart and effective way. Adv. Healthc. Mater. 2019, 8, 1801381–1801405.

    Article  CAS  Google Scholar 

  5. Cheung, R. C. F.; Wong, J. H.; Pan, W. L.; Chan, Y. S.; Yin, C. M.; Dan, X. L.; Wang, H. X.; Fang, E. F.; Lam, S. K.; Ngai, P. H. K.; Xia, L. X.; Liu, F.; Ye, X. Y.; Zhang, G. Q.; Liu, Q. H.; Sha, O.; Lin, P.; Ki, C.; Bekhit, A. A.; Bekhit, A. E. D.; Wan, D. C. C.; Ye, X. J.; Xia, J.; Ng, T. B. Antifungal and antiviral products of marine organisms. Appl. Microbiol. Biotechnol. 2014, 98, 3475–3494.

    Article  CAS  Google Scholar 

  6. Kooa, H.; Allanb, R. N.; Howlind, R. P.; Hall-Stoodleye, L.; Stoodley, P. Targeting microbial biofilms: Current and prospective therapeutic strategies. Nat. Rev. Microbiol. 2017, 15, 740–755.

    Article  Google Scholar 

  7. Kim, S. K.; Lee, J. H. Biofilm dispersion in Pseudomonas aeruginosa. J. Microbiol. 2016, 54, 71–85.

    Article  CAS  Google Scholar 

  8. Jian, J. R.; Jie, Y. S.; Mei, T. L.; Ai, X. S.; Rong, X. Z.; Fang, L. S.; Hua, Y. J.; Quan, R. L.; Jie, Z. A biomimetic surface for infection-resistance through assembly of metal-phenolic networks. Chinese J. Polym. Sci. 2018, 36, 576–583.

    Article  Google Scholar 

  9. Vögeling, H.; Pinnapireddy, S. R.; Seitz, B.; Bakowsky, U. Indocyanine green loaded PLGA film coated coronary stents for photo-triggered in situ biofilm eradication. Colloid Interface Sci. Commun. 2018, 27, 35–39.

    Article  Google Scholar 

  10. Reffuveille, F.; Fuente-Núñez, C. D. L.; Mansour, S.; Hancock, R. E. W. A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms. Antimicrob. Agents Chemother. 2014, 58, 5363–5371.

    Article  Google Scholar 

  11. Uppu, D. S. S. M.; Konai, M. M.; Sarkar, P.; Samaddar, S.; Fensterseifer, I. C. M.; Farias-Junior, C.; Krishnamoorthy, P.; Shome, B. R.; Franco, O. V. L.; Haldar, J. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards gram-negative bacteria. PLoS One 2017, 12, 1–30.

    Article  Google Scholar 

  12. Li, X. H.; Lee, J. H. Antibiofilm agents: A new perspective for antimicrobial strategy. J. Microbiol. 2017, 55, 753–766.

    Article  CAS  Google Scholar 

  13. Amato, S. M.; Fazen, C. H.; Henry, T. C.; Mok, W. K.; Orman, M. A.; Sandvik, E. L.; Volzing, K. G.; Brynildsen, M. The role of metabolism in bacterial persistence. Front. Microbiol. 2014, 5, 1–9.

    Article  Google Scholar 

  14. Balaban, N. Q.; Gerdes, K.; Lewis, K.; McKinney, J. D. A problem of persistence: Still more questions than answers? Nat. Rev. Microbiol. 2013, 11, 587–591.

    Article  CAS  Google Scholar 

  15. Kumagai, Y.; Matsuo, J.; Cheng, Z.; Yoshihiro; Hayakawa; Rikihisa, Y. Cyclic dimeric GMP signaling regulates intracellular aggregation, sessility, and growth of Ehrlichia chaffeensis. Infect. Immun. 2011, 79, 3905–3912.

    Article  CAS  Google Scholar 

  16. Lewis, K. Persister cells. Annu. Rev. Microbiol. 2010, 64, 357–372.

    Article  CAS  Google Scholar 

  17. Balaban, N. Q.; Merrin, J.; Chait, R.; Kowalik, L.; Leibler, S. Bacterial persistence as a phenotypic switch. Science 2004, 305, 1622–1626.

    Article  CAS  Google Scholar 

  18. Jie, Z. Y.; Sheng, H. S.; Zhong, D. J. ε-Poly(L-lysine)-based hydrogels with fast-acting and prolonged antibacterial activities. Chinese J. Polym. Sci. 2018, 36, 1239–1250.

    Article  Google Scholar 

  19. Chua, S. L.; Yam, J. K. H.; Hao, P.; Adav, S. S.; Salido, M. M.; Liu, Y.; Givskov, M.; Sze, S. K.; Tolker-Nielsen, T.; Yang, L. Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Nat. Commun. 2016, 7, 10750–10760.

    Article  CAS  Google Scholar 

  20. Yang, Q.; Li, M.; Spiller, O. B.; Andrey, D. O.; Hinchliffe, P.; Li, H.; MacLean, C.; Niumsup, P.; Powell, L.; Pritchard, M.; Papkou, A.; Shen, Y.; Portal, E.; Sands, K.; Spencer, J.; Tansawai, U.; Thomas, D.; Wang, S.; Wang, Y.; Shen, J.; Walsh, T. Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms. Nat. Commun. 2017, 8, 2054–2066.

    Article  Google Scholar 

  21. Zhao, D.; Xu, X. D.; Yuan, S. S.; Yan, S. J.; Wang, X. H.; Luan, S. F.; Yin, J. H. Fouling-resistant behavior of liquid-infused porous slippery surfaces. Chinese J. Polym. Sci. 2017, 35, 887–896.

    Article  CAS  Google Scholar 

  22. Wu, J.; Zhang, C.; Xu, S.; Pang, X.; Cai, G.; Wang, J. Preparation of zwitterionic polymer-functionalized cotton fabrics and the performance of anti-biofouling and long-term biofilm resistance. Colloid Interface Sci. Commun. 2018, 24, 98–104.

    Article  Google Scholar 

  23. 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  Google Scholar 

  24. Nijnik, A.; Hancock, R. E. W. Host defence peptides: Antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic-resistant infections. Emerg. Health Threats J. 2009, 2, 1–7.

    Google Scholar 

  25. Yang, Y.; Cai, Z.; Huang, Z.; Tang, X.; Zhang, X. Antimicrobial cationic polymers: From structural design to functional control. Polym. J. 2017, 50, 33–44.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Liu, S. P.; Zhou, L.; Lakshminarayanan, R.; Beuerman, R. W. Multivalent antimicrobial peptides as therapeutics: Design principles and structural diversities. Int. J. Pept. Res. Ther. 2010, 16, 199–213.

    Article  Google Scholar 

  28. Lam, S. J.; Wong, E. H. H.; O’Brien-Simpson, N. M.; Pantarat, N.; Blencowe, A.; Reynolds, E. C.; Qiao, G. G. Bionano interaction study on antimicrobial star-shaped peptide polymer nanoparticles. ACS Appl. Mater. Interfaces 2016, 8, 33446–33456.

    Article  CAS  Google Scholar 

  29. Cuthbert, T. J.; Hisey, B.; Harrison, T. D.; Trant, J. F.; Gillies, E. R.; Ragogna, P. J. Surprising antibacterial activity and selectivity of hydrophilic polyphosphoniums featuring sugar and hydroxy substituents. Angew. Chem. Int. Ed. 2018, 57, 12707–12710.

    Article  CAS  Google Scholar 

  30. 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  Google Scholar 

  31. Ong, Z. Y.; Wiradharma, N.; Yang, Y. Y. Strategies employed in the design and optimization of synthetic antimicrobial peptide amphiphiles with enhanced therapeutic potentials. Adv. Drug Delivery Rev. 2014, 78, 28–45.

    Article  CAS  Google Scholar 

  32. Sang, P.; Shi, Y.; Teng, P.; Cao, A.; Xu, H.; Li, Q.; Cai, J. Antimicrobial AApeptides. Curr. Top. Med. Chem. 2017, 17, 1266–1279.

    Article  CAS  Google Scholar 

  33. Mowery, B. P.; Lee, S. E.; Kissounko, D. A.; Epand, R. F.; Epand, R. M.; Weisblum, B.; Stahl, S. S.; Gellman, S. H. Mimicry of antimicrobial host-defense peptides by random copolymers. J. Am. Chem. Soc. 2007, 129, 15474–15476.

    Article  CAS  Google Scholar 

  34. Yang, L. H.; Gordon, V. D.; Mishra, A.; Som, A.; Purdy K. R.; Davis, M. A.; Tew, G. N.; Gerard C. L. W. Synthetic antimicrobial oligomers induce a composition-dependent topological transition in membranes. J. Am. Chem. Soc. 2007, 129, 12141–12147.

    Article  CAS  Google Scholar 

  35. Lienkamp, K.; Madkour, A. E.; Musante, A.; Nelson, C. F.; Sslein, K. N.; Tew, G. N. Antimicrobial polymers prepared by ROMP with unprecedented selectivity: A molecular construction kit approach. J. Am. Chem. Soc. 2008, 130, 9836–9843.

    Article  CAS  Google Scholar 

  36. Tew, G. N.; Scott, R. W.; Klein, M. L.; Degrado, W. F. De novo design of antimicrobial polymers, foldamers, and small molecules: From discovery to practical applications. Acc. Chem. Res. 2010, 43, 30–39.

    Article  CAS  Google Scholar 

  37. Liu, R.; Chen, X.; Falk, S. P.; Mowery, B. P.; Karlsson, A. J.; Weisblum, B.; Palecek, S. P.; Masters, K. S.; Gellman, S. H. Structure-activity relationships among antifungal Nylon-3 polymers: Identification of materials active against drug-resistant strains of Candida albicans. J. Am. Chem. Soc. 2014, 136, 4333–4342.

    Article  CAS  Google Scholar 

  38. Qian, Y.; Qi, F.; Chen, Q.; Zhang, Q.; Qiao, Z.; Zhang, S.; Wei, T.; Yu, Q.; Yu, S.; Mao, Z.; Gao, C.; Ding, Y.; Cheng, Y.; Jin, C.; Xie, H.; Liu, R. Surface modified with a host defense peptide-mimicking β-peptide polymer kills bacteria on contact with high efficacy. ACS Appl. Mater. Interfaces 2018, 10, 15395–15400.

    Article  CAS  Google Scholar 

  39. Zhang, D.; Qian, Y.; Zhang, S.; Ma, P.; Zhang, Q.; Shao, N.; Qi, F.; Xie, J.; Dai, C.; Zhou, R.; Qiao, Z.; Zhang, W.; Sheng, C.; Runhui, L. α-β Chimeric polypeptide molecular brushes display potent activity against superbugs-methicillin resistant Staphylococcus aureus. Sci. China Mater. 2018, 21, 1–7.

    Google Scholar 

  40. Verduzco, R.; Li, X.; Peseka, S. L.; Stein, G. E. Structure, function, self-assembly, and applications of bottlebrush copolymers. Chem. Soc. Rev. 2015, 44, 2405–2420.

    Article  CAS  Google Scholar 

  41. Zhang, M.; Müller, A. H. E. Cylindrical polymer brushes. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 3461–3481.

    Article  CAS  Google Scholar 

  42. Sheiko, S. S.; Sumerlin, B. S.; Matyjaszewski, K. Cylindrical molecular brushes: Synthesis, characterization, and properties. Prog. Polym. Sci. 2008, 33, 759–785.

    Article  CAS  Google Scholar 

  43. Lu, X.; Tran, T. H.; Jia, F.; Tan, X.; Davis, S.; Krishnan, S.; Amiji, M. M.; Zhang, K. Providing oligonucleotides with steric selectivity by brush-polymer-assisted compaction. J. Am. Chem. Soc. 2015, 137, 12466–12469.

    Article  CAS  Google Scholar 

  44. Wang, J.; Lu, H.; Ren, Y.; Zhang, Y.; Morton, M.; Cheng, J.; Lin, Y. Interrupted helical structure of grafted polypeptides in brush-like macromolecules. Macromolecules 2011, 44, 8699–8708.

    Article  CAS  Google Scholar 

  45. Zhang, Y.; Yin, Q.; Lu, H.; Xia, H.; Lin, Y.; Cheng, J. PEG-polypeptide dual brush block copolymers: Synthesis and application in nanoparticle surface PEGylation. ACS Macro Lett. 2013, 2, 809–813.

    Article  CAS  Google Scholar 

  46. Li, Z. Synthesis of hetero-grafted amphiphilic diblock molecular brushes and their self-assembly in aqueous medium. Macromolecules 2010, 43, 1182–1184.

    Article  CAS  Google Scholar 

  47. Fan, J.; Borguet, Y. P.; Su, L.; Nguyen, T. P.; Wang, H.; He, X.; Zou, J.; Woole, K. L. Two-dimensional controlled syntheses of polypeptide molecular brushes via N-carboxyanhydride ring-opening polymerization and ring-opening metathesis polymerization. ACS Macro Lett. 2017, 6, 1031–1035.

    Article  CAS  Google Scholar 

  48. Gao, Q.; Yu, M.; Su, Y. J.; Xie, M. H.; Zhao, X.; Li, P.; Ma, P. X. Rationally designed dual functional block copolymers for bottlebrush-like coatings: In vitro and in vivo antimicrobial, antibiofilm, and antifouling properties. Acta Biomater. 2017, 51, 112–124.

    Article  CAS  Google Scholar 

  49. Elshaarawya, R. F. M.; Refaeec, A. A.; El-Sawi, E. A. Pharmacological performance of novel poly-(ionic liquid)-grafted chitosan-N-salicylidene Schiff bases and their complexes. Carbohydr. Polym. 2016, 146, 376–387.

    Article  Google Scholar 

  50. Rahman, M. A.; Bam, M.; Luat, E.; Jui, M. S.; Ganewatta, M. S.; Shokfai, T.; Nagarkatti, M.; Decho, A. W.; Tang, C. Macromolecular-clustered facial amphiphilic antimicrobials. Nat. Commun. 2018, 9, 5231–5240.

    Article  Google Scholar 

  51. Vincek, M. K.; Mor, A.; Gorgieva, S.; Kokol, V. Antibacterial activity and cytotoxycity of gelatine-conjugated lysine-based peptides. J. Biomed. Mater. Res., Part A 2017, 105, 3110–3126.

    Article  Google Scholar 

  52. Yao, D.; Guo, Y.; Chen, S.; Tang, J.; Chen, Y. Shaped core/shell polymer nanoobjects with high antibacterial activities via block copolymer microphase separation. Polymer 2013, 54, 3485–3491.

    Article  CAS  Google Scholar 

  53. Yang, C.; Ding, X.; Ono, R. J.; Lee, H.; Hsu, L. Y.; Tong, Y. W.; Hedrick, J.; Yang, Y. Y. Brush-like polycarbonates containing dopamine, cations, and PEG providing a broad-spectrum, antibacterial, and antifouling surface via one-step coating. Adv. Mater. 2014, 26, 7346–7351.

    Article  CAS  Google Scholar 

  54. Mohamed, M. F.; Brezden, A.; Mohammad, H.; Chmielewski, J.; Seleem, M. N. A short D-enantiomeric antimicrobial peptide with potent immunomodulatory and antibiofilm activity against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Sci. Rep. 2017, 7, 6953.

    Article  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Nos. 21574038, 21774031, and 21861162010), the Natural Science Foundation of Shanghai (No. 18ZR1410300), the “Eastern Scholar Professorship” from Shanghai local government (No. TP2014034), the national special fund for State Key Laboratory of Bioreactor Engineering (No. 2060204), and the Fundamental Research Funds for the Central Universities (No. 22221818014).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Run-Hui Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, S., Xiao, XM., Qi, F. et al. Biofilm Disruption Utilizing α/β Chimeric Polypeptide Molecular Brushes. Chin J Polym Sci 37, 1105–1112 (2019). https://doi.org/10.1007/s10118-019-2278-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10118-019-2278-0

Keywords

Navigation