Issue

Vol. 12 (2020)

Multi-targeted Antisense Oligonucleotide Delivery by a Framework Nucleic Acid for Inhibiting Biofilm Formation and Virulence

https://doi.org/10.1007/s40820-020-0409-3
Yuxin Zhang
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
Xueping Xie
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
Wenjuan Ma
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
Yuxi Zhan
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
Chenchen Mao
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
Xiaoru Shao
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China
Yunfeng Lin
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, People’s Republic of China

Corresponding Author: Yunfeng Lin

yunfenglin@scu.edu.cn

Nano-Micro Letters, Vol. 12 (2020), Article Number: 74

Abstract

Biofilm formation is responsible for numerous chronic infections and represents a serious health challenge. Bacteria and the extracellular polysaccharides (EPS) cause biofilms to become adherent, toxic, resistant to antibiotics, and ultimately difficult to remove. Inhibition of EPS synthesis can prevent the formation of bacterial biofilms, reduce their robustness, and promote removal. Here, we have developed a framework nucleic acid delivery system with a tetrahedral configuration. It can easily access bacterial cells and functions by delivering antisense oligonucleotides that target specific genes. We designed antisense oligonucleotide sequences with multiple targets based on conserved regions of the VicK protein-binding site. Once delivered to bacterial cells, they significantly decreased EPS synthesis and biofilm thickness. Compared to existing approaches, this system is highly efficacious because it simultaneously reduces the expression of all targeted genes (gtfBCD, gbpB, ftf). We demonstrate a novel nucleic acid-based nanomaterial with multi-targeted inhibition that has great potential for the treatment of chronic infections caused by biofilms.


Highlights:


1 A framework nucleic acid delivery system was developed through self-assembly, which can deliver antisense oligonucleotides against multiple targets in bacterial cells.
2 The ASOs-tFNAs (750 nM) was found to simultaneously inhibit the expression of gtfBCD, gbpB, and ftf, and significantly reduce the extracellular polysaccharide synthesis and biofilm thickness.

Keywords

Biofilm Framework nucleic acid Multi-targeting Antisense oligonucleotide Delivery system
Zhang, Yuxin, Xueping Xie, Wenjuan Ma, Yuxi Zhan, Chenchen Mao, Xiaoru Shao, and Yunfeng Lin. 2020. “Multi-Targeted Antisense Oligonucleotide Delivery by a Framework Nucleic Acid for Inhibiting Biofilm Formation and Virulence”. Nano-Micro Letters 12 (March):74. https://doi.org/10.1007/s40820-020-0409-3.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. K. Lewis, Persister cells, dormancy and infectious disease. Nat. Rev. Microbiol. 5(1), 48–56 (2007). https://doi.org/10.1038/nrmicro1557
  2. L. Hall-Stoodley, J.W. Costerton, P. Stoodley, Bacterial biofilms: from the natural environment to infectious diseases. Nat. Rev. Microbiol. 2(2), 95–108 (2004). https://doi.org/10.1038/nrmicro821
  3. J.W. Costerton, P.S. Stewart, E.P. Greenberg, Bacterial biofilms: a common cause of persistent infections. Science 284(5418), 1318–1322 (1999). https://doi.org/10.1126/science.284.5418.1318
  4. S. Neethirajan, M.A. Clond, A. Vogt, Medical biofilms—nanotechnology approaches. J. Biomed. Nanotechnol. 10(10), 2806–2827 (2014). https://doi.org/10.1166/jbn.2014.1892
  5. X. Ning, S. Lee, Z. Wang, D. Kim, B. Stubblefield, E. Gilbert, N. Murthy, Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity. Nat. Mater. 10(8), 602–607 (2011). https://doi.org/10.1038/nmat3074
  6. J.P. Hegarty, D.B. Stewart Sr., Advances in therapeutic bacterial antisense biotechnology. Appl. Microbiol. Biotechnol. 102(3), 1055–1065 (2018). https://doi.org/10.1007/s00253-017-8671-0
  7. J.W. Costerton, J.C. Post, G.D. Ehrlich, F.Z. Hu, R. Kreft et al., New methods for the detection of orthopedic and other biofilm infections. FEMS Immunol. Med. Microbiol. 61(2), 133–140 (2011). https://doi.org/10.1111/j.1574695X.2010.00766.x
  8. A. Gupta, R. Das, G. Yesilbag Tonga, T. Mizuhara, V.M. Rotello, Charge-switchable nanozymes for bioorthogonal imaging of biofilm-associated infections. ACS Nano 12(1), 89–94 (2018). https://doi.org/10.1021/acsnano.7b07496
  9. H. Koo, R.N. Allan, R.P. Howlin, P. Stoodley, L. Hall-Stoodley, Targeting microbial biofilms: current and prospective therapeutic strategies. Nat. Rev. Microbiol. 15(12), 740–755 (2017). https://doi.org/10.1038/nrmicro.2017.99
  10. E.E. Mann, D.J. Wozniak, Pseudomonas biofilm matrix composition and niche biology. FEMS Microbiol. Rev. 36(4), 893–916 (2012). https://doi.org/10.1111/j.1574-6976.2011.00322.x
  11. S.A. Tursi, C. Tukel, Curli-containing enteric biofilms inside and out: matrix composition, immune recognition, and disease implications. Microbiol. Mol. Bio. Rev. 82(4), e00028–18 (2018). https://doi.org/10.1128/MMBR.00028-18
  12. Y. Zhang, W. Ma, Y. Zhu, S. Shi, Q. Li et al., Inhibiting methicillin-resistant Staphylococcus aureus by tetrahedral DNA nanostructure-enabled antisense peptide nucleic acid delivery. Nano Lett. 18(9), 5652–5659 (2018). https://doi.org/10.1021/acs.nanolett.8b02166
  13. H. Pei, X. Zuo, D. Zhu, Q. Huang, C. Fan, Functional DNA nanostructures for theranostic applications. Acc. Chem. Res. 47(2), 550–559 (2014). https://doi.org/10.1021/ar400195t
  14. J. Chao, H. Liu, S. Su, L. Wang, W. Huang, C. Fan, Structural DNA nanotechnology for intelligent drug delivery. Small 10(22), 4626–4635 (2014). https://doi.org/10.1002/smll.201401309
  15. L. Zhang, D. Pornpattananangku, C.M. Hu, C.M. Huang, Development of nanoparticles for antimicrobial drug delivery. Curr. Med. Chem. 17(6), 585–594 (2010). https://doi.org/10.2174/092986710790416290
  16. Q. Hu, H. Li, L. Wang, DNA nanotechnology-enabled drug delivery systems. Chem. Rev. 119(10), 6459–6506 (2018). https://doi.org/10.1021/acs.chemrev.7b00663
  17. M. Zhou, N.X. Liu, S.R. Shi, Y. Li, Q. Zhang et al., Effect of tetrahedral DNA nanostructures on proliferation and osteo/odontogenic differentiation of dental pulp stem cells via activation of the notch signaling pathway. Nanomed. Nanotechnol. Biol. Med. 14(4), 1227–1236 (2018). https://doi.org/10.1016/j.nano.2018.02.004
  18. X. Shao, S. Lin, Q. Peng, S. Shi, X. Wei, T. Zhang, Y. Lin, Tetrahedral DNA nanostructure: a potential promoter for cartilage tissue regeneration via regulating chondrocyte phenotype and proliferation. Small 13(12), 1602770 (2017). https://doi.org/10.1002/smll.201602770
  19. D. Zeng, Z. Wang, Z. Meng, P. Wang, L. San et al., DNA tetrahedral nanostructure-based electrochemical miRNA biosensor for simultaneous detection of multiple miRNAs in pancreatic carcinoma. ACS Appl. Mater. Interfaces 9(28), 24118–24125 (2017). https://doi.org/10.1021/acsami.7b05981
  20. D. Jiang, Y. Sun, J. Li, Q. Li, M. Lv et al., Multiple-armed tetrahedral DNA nanostructures for tumor-targeting, dual-modality in vivo imaging. ACS Appl. Mater. Interfaces 8(7), 4378–4384 (2016). https://doi.org/10.1021/acsami.5b10792
  21. Y. Zhang, Z. Cui, H. Kong, K. Xia, L. Pan et al., One-shot immunomodulatory nanodiamond agents for cancer immunotherapy. Adv. Mater. 28(14), 2699–2708 (2016). https://doi.org/10.1002/adma.201506232
  22. Q. Zhang, S. Lin, S. Shi, T. Zhang, Q. Ma et al., Anti-inflammatory and antioxidative effects of tetrahedral DNA nanostructures via the modulation of macrophage responses. ACS Appl. Mater. Interfaces 10(4), 3421–3430 (2018). https://doi.org/10.1021/acsami.7b17928
  23. Q. Li, D. Zhao, X. Shao, S. Lin, X. Xie et al., Aptamer-modified tetrahedral DNA nanostructure for tumor-targeted drug delivery. ACS Appl. Mater. Interfaces 9(42), 36695–36701 (2017). https://doi.org/10.1021/acsami.7b13328
  24. D. Ye, X. Zuo, C. Fan, DNA nanotechnology-enabled interfacial engineering for biosensor development. Ann. Rev. Anal. Chem. 11, 171–195 (2018). https://doi.org/10.1146/annurev-anchem-061417-010007
  25. S. Grijalvo, A. Alagia, A.F. Jorge, Covalent strategies for targeting messenger and non-coding RNAs: an updated review on siRNA, miRNA and antimiR conjugates. Genes 9(2), 74 (2018). https://doi.org/10.3390/genes9020074
  26. B. Soder, M. Yakob, J.H. Meurman, L.C. Andersson, P.O. Soder, The association of dental plaque with cancer mortality in Sweden. A longitudinal study. BMJ Open 2(3), e001083 (2012). https://doi.org/10.1136/bmjopen-2012-001083
  27. Y.H. Li, N. Tang, M.B. Aspiras, P.C. Lau, J.H. Lee, R.P. Ellen, D.G. Cvitkovitch, A quorum-sensing signaling system essential for genetic competence in Streptococcus mutans is involved in biofilm formation. J. Bacteriol. 184(10), 2699–2708 (2002). https://doi.org/10.1128/JB.184.10.2699-2708.2002
  28. J.B. Kaplan, Biofilm matrix-degrading enzymes. Methods Mol. Biol. 1147, 203–213 (2014). https://doi.org/10.1007/978-1-4939-0467-9_14
  29. D. Viszwapriya, G.A. Subramenium, S. Radhika, S.K. Pandian, Betulin inhibits cariogenic properties of Streptococcus mutans by targeting VicRK and gtf genes. Antonie Van Leeuwenhoek 110(1), 153–165 (2017). https://doi.org/10.1007/s10482-016-0785-3
  30. D.B. Senadheera, M. Cordova, E.A. Ayala, L.E. Chavez de Paz, K. Singh et al., Regulation of bacteriocin production and cell death by the VicRK signaling system in Streptococcus mutans. J. Bacteriol. 194(6), 1307–1316 (2012). https://doi.org/10.1128/JB.06071-11
  31. L.A. Alves, E.N. Harth-Chu, T.H. Palma, R.N. Stipp, F.S. Mariano et al., The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity. Mol. Oral Microbiol. 32(5), 419–431 (2017). https://doi.org/10.1111/omi.12183
  32. M.D. Senadheera, B. Guggenheim, G.A. Spatafora, Y.C. Huang, J. Choi et al., A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J. Bacteriol. 187(12), 4064–4076 (2005). https://doi.org/10.1128/JB.187.12.4064-4076.2005
  33. R.N. Stipp, H. Boisvert, D.J. Smith, J.F. Hofling, M.J. Duncan, R.O. Mattos-Graner, CovR and VicRK regulate cell surface biogenesis genes required for biofilm formation in Streptococcus mutans. PLoS One 8(3), e58271 (2013). https://doi.org/10.1371/journal.pone.0058271
  34. S. Dubrac, T. Msadek, Identification of genes controlled by the essential YycG/YycF two-component system of Staphylococcus aureus. J. Bacteriol. 186(4), 1175–1181 (2004). https://doi.org/10.1128/JB.186.4.1175-1181.2004
  35. G. Zhao, J. Li, Z. Tong, B. Zhao, R. Mu, Y. Guan, Enzymatic cleavage of type II restriction endonucleases on the 2′-o-methyl nucleotide and phosphorothioate substituted DNA. PLoS One 8(11), e79415 (2013). https://doi.org/10.1371/journal.pone.0079415
  36. I. Charles, E. Davis, D.P. Arya, Efficient stabilization of phosphodiester (PO), phosphorothioate (PS), and 2′-o-methoxy (2′-ome) DNA. RNA hybrid duplexes by amino sugars. Biochemistry 51(27), 5496–5505 (2012). https://doi.org/10.1021/bi3004507
  37. X. Piao, H. Wang, D.W. Binzel, P. Guo, Assessment and comparison of thermal stability of phosphorothioate-DNA, DNA, RNA, 2′-F RNA, and LNA in the context of Phi29 pRNA 3WJ. RNA 24(1), 67–76 (2018). https://doi.org/10.1261/rna.063057.117
  38. S. Shi, S. Lin, X. Shao, Q. Li, Z. Tao, Y. Lin, Modulation of chondrocyte motility by tetrahedral DNA nanostructures. Cell Prolif. 50(5), e12368 (2017). https://doi.org/10.1111/cpr.12368
  39. X. Xie, X. Shao, W. Ma, D. Zhao, S. Shi, Q. Li, Y. Lin, Overcoming drug-resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures. Nanoscale 10(12), 5457–5465 (2018). https://doi.org/10.1039/c7nr09692e
  40. W. Ma, S.X. Hao, D. Zhao, Q. Li, M. Liu, T. Zhou, X. Xie, C. Mao, Y. Zhang, Y. Lin, Self-assembled tetrahedral DNA nanostructures promote neural stem cell proliferation and neuronal differentiation. ACS Appl. Mater. Interfaces 10(9), 7892–7900 (2018). https://doi.org/10.1021/acsami.8b00833
  41. A. Dell’Anno, M. Fabiano, G.C.A. Duineveld, A. Kok, R. Danovaro, Nucleic acid (DNA, RNA) quantification and RNA/DNA ratio determination in marine sediments: comparison of spectrophotometric, fluorometric, and highperformance liquid chromatography methods and estimation of detrital DNA. Appl. Environ. Microbiol. 64(9), 3238–3245 (1998). https://doi.org/10.1128/AEM.64.9.32383245.1998
  42. Q. Hu, S. Wang, L. Wang, H. Gu, C. Fan, DNA nanostructure-based systems for intelligent delivery of therapeutic oligonucleotides. Adv. Healthc. Mater. 7(20), 1701153 (2018). https://doi.org/10.1002/adhm.201701153
  43. X. Liu, Y. Gao, X. Wang, S. Wu, Z. Tang, Preparation of stable, water-soluble, highly luminescence quantum dots with small hydrodynamic sizes. J. Nanosci. Nanotechnol. 11(3), 1941–1949 (2011). https://doi.org/10.1166/jnn.2011.3531
  44. P. Ommen, N. Zobek, R.L. Meyer, Quantification of biofilm biomass by staining: non-toxic safranin can replace the popular crystal violet. J. Microbiol. Methods 141, 87–89 (2017). https://doi.org/10.1016/j.mimet.2017.08.003
  45. K. Ivanova, M.M. Fernandes, A. Francesko, E. Mendoza, J. Guezguez, M. Burnet, T. Tzanov, Quorum-quenching and matrix-degrading enzymes in multilayer coatings synergistically prevent bacterial biofilm formation on urinary catheters. ACS Appl. Mater. Interfaces 7(49), 27066–27077 (2015). https://doi.org/10.1021/acsami.5b09489
  46. M.I. Klein, S. Duarte, J. Xiao, S. Mitra, T.H. Foster, H. Koo, Structural and molecular basis of the role of starch and sucrose in Streptococcus mutans biofilm development. Appl. Environ. Microbiol. 75(3), 837–841 (2009). https://doi.org/10.1128/AEM.01299-08
  47. S. Sharma, S. Lavender, J. Woo, L. Guo, W. Shi, L. Kilpatrick-Liverman, J.K. Gimzewski, Nanoscale characterization of effect of l-arginine on Streptococcus mutans biofilm adhesion by atomic force microscopy. Microbiology 160(Pt 7), 1466–1473 (2014). https://doi.org/10.1099/mic.0.075267-0
  48. R.M. Murata, L.S. Branco-de-Almeida, E.M. Franco, R. Yatsuda, M.H. dos Santos, S.M. de Alencar, H. Koo, P.L. Rosalen, Inhibition of Streptococcus mutans biofilm accumulation and development of dental caries in vivo by 7-epiclusianone and fluoride. Biofouling 26(7), 865–872 (2010). https://doi.org/10.1080/08927014.2010.527435
  49. A. Yanagida, T. Kanda, M. Tanabe, F. Matsudaira, J.G. Oliveira Cordeiro, Inhibitory effects of apple polyphenols and related compounds on cariogenic factors of mutans streptococci. J. Agric. Food Chem. 48(11), 5666–5671 (2000). https://doi.org/10.1021/jf000363i
  50. E.G. Smith, G.A. Spatafora, Gene regulation in S. mutans: complex control in a complex environment. J. Dent. Res. 91(2), 133–141 (2012). https://doi.org/10.1177/0022034511415415
  51. A. Heydorn, A.T. Nielsen, R.M. Hentze, C. Sternberg, M. Givskov, B.K. Ersboll, S. Molin, Quantification of biofilm structures by the novel computer program COMSTAT. Microbiology 146, 2395–2407 (2000). https://doi.org/10.1099/00221287-146-10-2395
Read More
Author biographies are not available.
Download this PDF file
PDF
Statistic
Read Counter : 4432 Download : 3355

Most read articles by the same author(s)