Advertisement

Strategies for the Eradication of Biofilm-Based Bacterial Infections

  • Roberta J. Melander
  • Christian MelanderEmail author
Chapter

Abstract

Biofilm-based bacterial infections are a significant health threat due to their chronic nature and lack of susceptibility to both the host immune response and to treatment with conventional antibiotics. There are numerous complex and interrelated mechanisms underling this tolerance, and strategies to overcome them are required in order to combat the considerable threat posed by biofilm-based bacterial infections. Several such strategies that have been explored toward the eradication of biofilm-based bacterial infections are discussed in this chapter. One strategy involves developing new antibiotics that are active against biofilm cells, while other approaches center on enhancing the activity of conventional antibiotics against biofilm cells with compounds that interfere with quorum sensing and other bacterial signaling and communication pathways, target biofilm-specific genes, or target the biofilm matrix.

Keywords

Biofilm Antibiotic Tolerance Matrix Adjuvant 

References

  1. Alipour, M., Suntres, Z. E., & Omri, A. (2009). Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa. The Journal of Antimicrobial Chemotherapy, 64(2), 317–325.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Amara, N., Mashiach, R., Amar, D., Krief, P., Spieser, S. A., Bottomley, M. J., Aharoni, A., & Meijler, M. M. (2009). Covalent inhibition of bacterial quorum sensing. Journal of the American Chemical Society, 131(30), 10610–10619.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Antoniani, D., Bocci, P., Maciag, A., Raffaelli, N., & Landini, P. (2010). Monitoring of diguanylate cyclase activity and of cyclic-di-GMP biosynthesis by whole-cell assays suitable for high-throughput screening of biofilm inhibitors. Applied Microbiology and Biotechnology, 85(4), 1095–1104.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Baldry, M., Kitir, B., Frokiaer, H., Christensen, S. B., Taverne, N., Meijerink, M., Franzyk, H., Olsen, C. A., Wells, J. M., & Ingmer, H. (2016). The agr inhibitors solonamide B and analogues alter immune responses to Staphylococccus aureus but do not exhibit adverse effects on immune cell functions. PLoS One, 11(1), e0145618.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ballard, T. E., Richards, J. J., Wolfe, A. L., & Melander, C. (2008). Synthesis and antibiofilm activity of a second-generation reverse-amide Oroidin library: A structure-activity relationship study. Chemistry—a European Journal, 14(34), 10745–10761.CrossRefGoogle Scholar
  6. Banu, L. D., Conrads, G., Rehrauer, H., Hussain, H., Allan, E., & van der Ploeg, J. R. (2010). The Streptococcus mutans serine/threonine kinase, PknB, regulates competence development, bacteriocin production, and cell wall metabolism. Infection and Immunity, 78(5), 2209–2220.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Barlow, M. (2009). What antimicrobial resistance has taught us about horizontal gene transfer. Methods in Molecular Biology, 532, 397–411.PubMedCrossRefPubMedCentralGoogle Scholar
  8. Baugh, S., Ekanayaka, A. S., Piddock, L. J., & Webber, M. A. (2012). Loss of or inhibition of all multidrug resistance efflux pumps of Salmonella enterica serovar typhimurium results in impaired ability to form a biofilm. The Journal of Antimicrobial Chemotherapy, 67(10), 2409–2417.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Baugh, S., Phillips, C. R., Ekanayaka, A. S., Piddock, L. J., & Webber, M. A. (2014). Inhibition of multidrug efflux as a strategy to prevent biofilm formation. The Journal of Antimicrobial Chemotherapy, 69(3), 673–681.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bayer, A. S., Park, S., Ramos, M. C., Nast, C. C., Eftekhar, F., & Schiller, N. L. (1992). Effects of alginase on the natural history and antibiotic therapy of experimental endocarditis caused by mucoid Pseudomonas aeruginosa. Infection and Immunity, 60(10), 3979–3985.PubMedPubMedCentralGoogle Scholar
  11. Bijtenhoorn, P., Schipper, C., Hornung, C., Quitschau, M., Grond, S., Weiland, N., & Streit, W. R. (2011). BpiB05, a novel metagenome-derived hydrolase acting on N-acylhomoserine lactones. Journal of Biotechnology, 155(1), 86–94.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Bjarnsholt, T. (2013). The role of bacterial biofilms in chronic infections. APMIS. Supplementum, 136, 1–51.CrossRefGoogle Scholar
  13. Blazquez, J. (2003). Hypermutation as a factor contributing to the acquisition of antimicrobial resistance. Clinical Infectious Diseases, 37(9), 1201–1209.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Boles, B. R., & Horswill, A. R. (2008). Agr-mediated dispersal of Staphylococcus aureus biofilms. PLoS Pathogens, 4(4), e1000052.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Brackman, G., Breyne, K., De Rycke, R., Vermote, A., Van Nieuwerburgh, F., Meyer, E., Van Calenbergh, S., & Coenye, T. (2016). The quorum sensing inhibitor Hamamelitannin increases antibiotic susceptibility of Staphylococcus aureus biofilms by affecting peptidoglycan biosynthesis and eDNA release. Scientific Reports, 6, 20321.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Brackman, G., Cos, P., Maes, L., Nelis, H. J., & Coenye, T. (2011). Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrobial Agents and Chemotherapy, 55(6), 2655–2661.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Brotz-Oesterhelt, H., Beyer, D., Kroll, H. P., Endermann, R., Ladel, C., Schroeder, W., Hinzen, B., Raddatz, S., Paulsen, H., Henninger, K., Bandow, J. E., Sahl, H. G., & Labischinski, H. (2005). Dysregulation of bacterial proteolytic machinery by a new class of antibiotics. Nature Medicine, 11(10), 1082–1087.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Bunders, C., Cavanagh, J., & Melander, C. (2011a). Flustramine inspired synthesis and biological evaluation of pyrroloindoline triazole amides as novel inhibitors of bacterial biofilms. Organic & Biomolecular Chemistry, 9(15), 5476–5481.CrossRefGoogle Scholar
  19. Bunders, C. A., Minvielle, M. J., Worthington, R. J., Ortiz, M., Cavanagh, J., & Melander, C. (2011b). Intercepting bacterial indole signaling with flustramine derivatives. Journal of the American Chemical Society, 133(50), 20160–20163.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Camilli, A., & Bassler, B. L. (2006). Bacterial small-molecule signaling pathways. Science, 311(5764), 1113–1116.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Coates, A. R., & Hu, Y. (2008). Targeting non-multiplying organisms as a way to develop novel antimicrobials. Trends in Pharmacological Sciences, 29(3), 143–150.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Conibear, T. C., Collins, S. L., & Webb, J. S. (2009). Role of mutation in Pseudomonas aeruginosa biofilm development. PLoS One, 4(7), e6289.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Conlon, B. P., Nakayasu, E. S., Fleck, L. E., LaFleur, M. D., Isabella, V. M., Coleman, K., Leonard, S. N., Smith, R. D., Adkins, J. N., & Lewis, K. (2013). Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature, 503(7476), 365–370.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Conlon, B. P., Rowe, S. E., & Lewis, K. (2015). Persister cells in biofilm associated infections. Advances in Experimental Medicine and Biology, 831, 1–9.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Darouiche, R. O., Mansouri, M. D., Gawande, P. V., & Madhyastha, S. (2009). Antimicrobial and antibiofilm efficacy of triclosan and DispersinB combination. The Journal of Antimicrobial Chemotherapy, 64(1), 88–93.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Davey, M. E., & O’Toole, G. A. (2000). Microbial biofilms: From ecology to molecular genetics. Microbiology and Molecular Biology Reviews, 64(4), 847–867.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Davies, D. (2003). Understanding biofilm resistance to antibacterial agents. Nature Reviews Drug Discovery, 2(2), 114–122.PubMedCrossRefPubMedCentralGoogle Scholar
  28. Di Luca, M., Maccari, G., & Nifosi, R. (2014). Treatment of microbial biofilms in the post-antibiotic era: Prophylactic and therapeutic use of antimicrobial peptides and their design by bioinformatics tools. Pathogens and Disease, 70(3), 257–270.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Donelli, G., Francolini, I., Romoli, D., Guaglianone, E., Piozzi, A., Ragunath, C., & Kaplan, J. B. (2007). Synergistic activity of dispersin B and cefamandole nafate in inhibition of staphylococcal biofilm growth on polyurethanes. Antimicrobial Agents and Chemotherapy, 51(8), 2733–2740.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Donlan, R. M. (2002). Biofilms: Microbial life on surfaces. Emerging Infectious Diseases, 8(9), 881–890.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Eguchi, Y., Kubo, N., Matsunaga, H., Igarashi, M., & Utsumi, R. (2011). Development of an antivirulence drug against Streptococcus mutans: Repression of biofilm formation, acid tolerance, and competence by a histidine kinase inhibitor, walkmycin C. Antimicrobial Agents and Chemotherapy, 55(4), 1475–1484.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Flemming, H. C., & Wingender, J. (2010). The biofilm matrix. Nature Reviews. Microbiology, 8(9), 623–633.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Frederiksen, B., Pressler, T., Hansen, A., Koch, C., & Hoiby, N. (2006). Effect of aerosolized rhDNase (Pulmozyme) on pulmonary colonization in patients with cystic fibrosis. Acta Paediatrica, 95(9), 1070–1074.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Frezza, M., Soulere, L., Balestrino, D., Gohar, M., Deshayes, C., Queneau, Y., Forestier, C., & Doutheau, A. (2007). Ac2-DPD, the bis-(O)-acetylated derivative of 4,5-dihydroxy-2,3-pentanedione (DPD) is a convenient stable precursor of bacterial quorum sensing autoinducer AI-2. Bioorganic & Medicinal Chemistry Letters, 17(5), 1428–1431.CrossRefGoogle Scholar
  35. Garrison, A. T., Abouelhassan, Y., Kallifidas, D., Bai, F., Ukhanova, M., Mai, V., Jin, S., Luesch, H., & Huigens, R. W., 3rd. (2015). Halogenated phenazines that potently eradicate biofilms, MRSA persister cells in non-biofilm cultures, and Mycobacterium tuberculosis. Angewandte Chemie (International Ed. in English), 54(49), 14819–14823.CrossRefGoogle Scholar
  36. Geske, G. D., Wezeman, R. J., Siegel, A. P., & Blackwell, H. E. (2005). Small molecule inhibitors of bacterial quorum sensing and biofilm formation. Journal of the American Chemical Society, 127(37), 12762–12763.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Gordon, C. P., Williams, P., & Chan, W. C. (2013). Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective. Journal of Medicinal Chemistry, 56(4), 1389–1404.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Grandclement, C., Tannieres, M., Morera, S., Dessaux, Y., & Faure, D. (2016). Quorum quenching: Role in nature and applied developments. FEMS Microbiology Reviews, 40(1), 86–116.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Guo, M., Gamby, S., Zheng, Y., & Sintim, H. O. (2013). Small molecule inhibitors of AI-2 signaling in bacteria: State-of-the-art and future perspectives for anti-quorum sensing agents. International Journal of Molecular Sciences, 14(9), 17694–17728.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Gutierrez, J. A., Crowder, T., Rinaldo-Matthis, A., Ho, M. C., Almo, S. C., & Schramm, V. L. (2009). Transition state analogs of 5 ’-methylthioadenosine nucleosidase disrupt quorum sensing. Nature Chemical Biology, 5(4), 251–257.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Hall, C. W., & Mah, T. F. (2017). Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiology Reviews, 41(3), 276–301.PubMedCrossRefPubMedCentralGoogle Scholar
  42. Hancock, V., Witso, I. L., & Klemm, P. (2011). Biofilm formation as a function of adhesin, growth medium, substratum and strain type. International Journal of Medical Microbiology, 301(7), 570–576.PubMedCrossRefPubMedCentralGoogle Scholar
  43. Hausner, M., & Wuertz, S. (1999). High rates of conjugation in bacterial biofilms as determined by quantitative in situ analysis. Applied and Environmental Microbiology, 65(8), 3710–3713.PubMedPubMedCentralGoogle Scholar
  44. Hentzer, M., Riedel, K., Rasmussen, T. B., Heydorn, A., Andersen, J. B., Parsek, M. R., Rice, S. A., Eberl, L., Molin, S., Hoiby, N., Kjelleberg, S., & Givskov, M. (2002). Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology-Sgm, 148, 87–102.CrossRefGoogle Scholar
  45. Hentzer, M., Wu, H., Andersen, J. B., Riedel, K., Rasmussen, T. B., Bagge, N., Kumar, N., Schembri, M. A., Song, Z. J., Kristoffersen, P., Manefield, M., Costerton, J. W., Molin, S., Eberl, L., Steinberg, P., Kjelleberg, S., Hoiby, N., & Givskov, M. (2003). Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO Journal, 22(15), 3803–3815.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Hoiby, N., Bjarnsholt, T., Moser, C., Bassi, G. L., Coenye, T., Donelli, G., Hall-Stoodley, L., Hola, V., Imbert, C., Kirketerp-Moller, K., Lebeaux, D., Oliver, A., Ullmann, A. J., Williams, C., Biofilms, E. S. G. F., & Z Consulting External Expert Werner. (2015). ESCMID guideline for the diagnosis and treatment of biofilm infections 2014. Clinical Microbiology and Infection, 21(Suppl 1), 1–25.CrossRefGoogle Scholar
  47. Hraiech, S., Hiblot, J., Lafleur, J., Lepidi, H., Papazian, L., Rolain, J. M., Raoult, D., Elias, M., Silby, M. W., Bzdrenga, J., Bregeon, F., & Chabriere, E. (2014). Inhaled lactonase reduces Pseudomonas aeruginosa quorum sensing and mortality in rat pneumonia. PLoS One, 9(10), e107125.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Hurdle, J. G., O’Neill, A. J., Chopra, I., & Lee, R. E. (2011). Targeting bacterial membrane function: An underexploited mechanism for treating persistent infections. Nature Reviews. Microbiology, 9(1), 62–75.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Itoh, Y., Wang, X., Hinnebusch, B. J., Preston, J. F., 3rd, & Romeo, T. (2005). Depolymerization of beta-1,6-N-acetyl-D-glucosamine disrupts the integrity of diverse bacterial biofilms. Journal of Bacteriology, 187(1), 382–387.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Iwase, T., Uehara, Y., Shinji, H., Tajima, A., Seo, H., Takada, K., Agata, T., & Mizunoe, Y. (2010). Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature, 465(7296), 346–349.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Izano, E. A., Amarante, M. A., Kher, W. B., & Kaplan, J. B. (2008). Differential roles of poly-N-acetylglucosamine surface polysaccharide and extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis biofilms. Applied and Environmental Microbiology, 74(2), 470–476.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Jani, S., Seely, A. L., Peabody, V. G., Jayaraman, A., & Manson, M. D. (2017). Chemotaxis to self-generated AI-2 promotes biofilm formation in Escherichia coli. Microbiology.  https://doi.org/10.1099/mic.0.000567.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Jefferson, K. K. (2004). What drives bacteria to produce a biofilm? FEMS Microbiology Letters, 236(2), 163–173.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Johansson, E. M., Crusz, S. A., Kolomiets, E., Buts, L., Kadam, R. U., Cacciarini, M., Bartels, K. M., Diggle, S. P., Camara, M., Williams, P., Loris, R., Nativi, C., Rosenau, F., Jaeger, K. E., Darbre, T., & Reymond, J. L. (2008). Inhibition and dispersion of Pseudomonas aeruginosa biofilms by glycopeptide dendrimers targeting the fucose-specific lectin LecB. Chemistry & Biology, 15(12), 1249–1257.CrossRefGoogle Scholar
  55. Kaplan, J. B. (2010). Biofilm dispersal: Mechanisms, clinical implications, and potential therapeutic uses. Journal of Dental Research, 89(3), 205–218.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kaplan, J. B., LoVetri, K., Cardona, S. T., Madhyastha, S., Sadovskaya, I., Jabbouri, S., & Izano, E. A. (2012). Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci. Journal of Antibiotics (Tokyo), 65(2), 73–77.CrossRefGoogle Scholar
  57. Kaplan, J. B., Ragunath, C., Velliyagounder, K., Fine, D. H., & Ramasubbu, N. (2004). Enzymatic detachment of Staphylococcus epidermidis biofilms. Antimicrobial Agents and Chemotherapy, 48(7), 2633–2636.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Kiran, M. D., Adikesavan, N. V., Cirioni, O., Giacometti, A., Silvestri, C., Scalise, G., Ghiselli, R., Saba, V., Orlando, F., Shoham, M., & Balaban, N. (2008). Discovery of a quorum-sensing inhibitor of drug-resistant staphylococcal infections by structure-based virtual screening. Molecular Pharmacology, 73(5), 1578–1586.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Kunze, B., Reck, M., Dotsch, A., Lemme, A., Schummer, D., Irschik, H., Steinmetz, H., & Wagner-Dobler, I. (2010). Damage of Streptococcus mutans biofilms by carolacton, a secondary metabolite from the myxobacterium Sorangium cellulosum. BMC Microbiology, 10, 199.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Lamppa, J. W., & Griswold, K. E. (2013). Alginate lyase exhibits catalysis-independent biofilm dispersion and antibiotic synergy. Antimicrobial Agents and Chemotherapy, 57(1), 137–145.PubMedPubMedCentralCrossRefGoogle Scholar
  61. Lee, J., Bansal, T., Jayaraman, A., Bentley, W. E., & Wood, T. K. (2007a). Enterohemorrhagic Escherichia coli biofilms are inhibited by 7-hydroxyindole and stimulated by isatin. Applied and Environmental Microbiology, 73(13), 4100–4109.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Lee, J., Jayaraman, A., & Wood, T. K. (2007b). Indole is an inter-species biofilm signal mediated by SdiA. BMC Microbiology, 7, 42.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Lee, J., & Lee, J. H. (2010). Indole as an intercellular signal in microbial communities. FEMS Microbiology Reviews, 34(4), 426–444.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Lee, J. H., Cho, M. H., & Lee, J. (2011). 3-indolylacetonitrile decreases Escherichia coli O157:H7 biofilm formation and Pseudomonas aeruginosa virulence. Environmental Microbiology, 13(1), 62–73.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Lee, J. H., Kim, Y. G., Cho, M. H., Kim, J. A., & Lee, J. (2012). 7-fluoroindole as an antivirulence compound against Pseudomonas aeruginosa. FEMS Microbiology Letters, 329(1), 36–44.PubMedCrossRefPubMedCentralGoogle Scholar
  66. Lewis, K. (2001). Riddle of biofilm resistance. Antimicrobial Agents and Chemotherapy, 45(4), 999–1007.PubMedPubMedCentralCrossRefGoogle Scholar
  67. Lieberman, O. J., Orr, M. W., Wang, Y., & Lee, V. T. (2014). High-throughput screening using the differential radial capillary action of ligand assay identifies ebselen as an inhibitor of diguanylate cyclases. ACS Chemical Biology, 9(1), 183–192.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Liu, C., Worthington, R. J., Melander, C., & Wu, H. (2014). A new small molecule specifically inhibits the cariogenic bacterium Streptococcus mutans in multispecies biofilms. Antimicrobial Agents and Chemotherapy, 55(6), 2679–2687.CrossRefGoogle Scholar
  69. Lonn-Stensrud, J., Petersen, F. C., Benneche, T., & Scheie, A. A. (2007). Synthetic bromated furanone inhibits autoinducer-2-mediated communication and biofilm formation in oral streptococci. Oral Microbiology and Immunology, 22(5), 340–346.PubMedCrossRefPubMedCentralGoogle Scholar
  70. Lyons, N. A., & Kolter, R. (2015). On the evolution of bacterial multicellularity. Current Opinion in Microbiology, 24, 21–28.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Mah, T. F. C., & O’Toole, G. A. (2001). Mechanisms of biofilm resistance to antimicrobial agents. Trends in Microbiology, 9(1), 34–39.PubMedCrossRefPubMedCentralGoogle Scholar
  72. Malone, C. L., Boles, B. R., & Horswill, A. R. (2007). Biosynthesis of Staphylococcus aureus the Synechocystis autoinducing peptides by using DnaB mini-intein. Applied and Environmental Microbiology, 73(19), 6036–6044.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Mansour, S. C., de la Fuente-Nunez, C., & Hancock, R. E. (2015). Peptide IDR-1018: Modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections. Journal of Peptide Science, 21(5), 323–329.PubMedCrossRefPubMedCentralGoogle Scholar
  74. Mattmann, M. E., & Blackwell, H. E. (2010). Small molecules that modulate quorum sensing and control virulence in Pseudomonas aeruginosa. The Journal of Organic Chemistry, 75(20), 6737–6746.PubMedPubMedCentralCrossRefGoogle Scholar
  75. May, J. G., Shah, P., Sachdeva, L., Micale, M., Kruper, G. J., Sheyn, A., & Coticchia, J. M. (2014). Potential role of biofilms in deep cervical abscess. International Journal of Pediatric Otorhinolaryngology, 78(1), 10–13.PubMedCrossRefPubMedCentralGoogle Scholar
  76. Melander, R. J., Liu, H. B., Stephens, M. D., Bewley, C. A., & Melander, C. (2016). Marine sponge alkaloids as a source of anti-bacterial adjuvants. Bioorganic & Medicinal Chemistry Letters, 26(24), 5863–5866.CrossRefGoogle Scholar
  77. Melander, R. J., Minvielle, M. J., & Melander, C. (2014). Controlling bacterial behavior with indole-containing natural products and derivatives. Tetrahedron, 70(37), 6363–6372.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Milton, M. E., Minrovic, B. M., Harris, D. L., Kang, B., Jung, D., Lewis, C. P., Thompson, R. J., Melander, R. J., Zeng, D., Melander, C., & Cavanagh, J. (2018). Re-sensitizing multidrug resistant Bacteria to antibiotics by targeting bacterial response regulators: Characterization and comparison of interactions between 2-Aminoimidazoles and the response regulators BfmR from Acinetobacter baumannii and QseB from Francisella spp. Frontiers in Molecular Biosciences, 5, 15.PubMedPubMedCentralCrossRefGoogle Scholar
  79. Minvielle, M. J., Bunders, C. A., & Melander, C. (2013a). Indole/triazole conjugates are selective inhibitors and inducers of bacterial biofilms. MedChemComm, 4(6), 916–919.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Minvielle, M. J., Eguren, K., & Melander, C. (2013b). Highly active modulators of indole signaling alter pathogenic behaviors in gram-negative and gram-positive bacteria. Chemistry, 19(51), 17595–17602.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Nikolaev Iu, A., & Plakunov, V. K. (2007). Biofilm—“City of microbes” or an analogue of multicellular organisms? Mikrobiologiia, 76(2), 149–163.PubMedPubMedCentralGoogle Scholar
  82. O’Loughlin, C. T., Miller, L. C., Siryaporn, A., Drescher, K., Semmelhack, M. F., & Bassler, B. L. (2013). A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proceedings of the National Academy of Sciences of the United States of America, 110(44), 17981–17986.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Oliver, A., Canton, R., Campo, P., Baquero, F., & Blazquez, J. (2000). High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science, 288(5469), 1251–1254.PubMedCrossRefPubMedCentralGoogle Scholar
  84. Pan, W., Fan, M., Wu, H., Melander, C., & Liu, C. (2015). A new small molecule inhibits Streptococcus mutans biofilms in vitro and in vivo. Journal of Applied Microbiology, 119(5), 1403–1411.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Parsek, M. R., & Greenberg, E. P. (2000). Acyl-homoserine lactone quorum sensing in gram-negative bacteria: A signaling mechanism involved in associations with higher organisms. Proceedings of the National Academy of Sciences of the United States of America, 97(16), 8789–8793.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Parsiegla, G., Noguere, C., Santell, L., Lazarus, R. A., & Bourne, Y. (2012). The structure of human DNase I bound to magnesium and phosphate ions points to a catalytic mechanism common to members of the DNase I-like superfamily. Biochemistry, 51(51), 10250–10258.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Passos da Silva, D., Schofield, M. C., Parsek, M. R., & Tseng, B. S. (2017). An update on the sociomicrobiology of quorum sensing in gram-negative biofilm development. Pathogens, 6(4), E51.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Peters, L., Konig, G. M., Wright, A. D., Pukall, R., Stackebrandt, E., Eberl, L., & Riedel, K. (2003). Secondary metabolites of Flustra foliacea and their influence on bacteria. Applied and Environmental Microbiology, 69(6), 3469–3475.PubMedPubMedCentralCrossRefGoogle Scholar
  89. Pletzer, D., Coleman, S. R., & Hancock, R. E. (2016). Anti-biofilm peptides as a new weapon in antimicrobial warfare. Current Opinion in Microbiology, 33, 35–40.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Poole, K. (2012). Bacterial stress responses as determinants of antimicrobial resistance. The Journal of Antimicrobial Chemotherapy, 67(9), 2069–2089.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Qi, F., Merritt, J., Lux, R., & Shi, W. (2004). Inactivation of the ciaH gene in Streptococcus mutans diminishes mutacin production and competence development, alters sucrose-dependent biofilm formation, and reduces stress tolerance. Infection and Immunity, 72(8), 4895–4899.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Qin, Z., Zhang, J., Xu, B., Chen, L., Wu, Y., Yang, X., Shen, X., Molin, S., Danchin, A., Jiang, H., & Qu, D. (2006). Structure-based discovery of inhibitors of the YycG histidine kinase: New chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiology, 6, 96.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Quave, C. L., Estevez-Carmona, M., Compadre, C. M., Hobby, G., Hendrickson, H., Beenken, K. E., & Smeltzer, M. S. (2012). Ellagic acid derivatives from Rubus ulmifolius inhibit Staphylococcus aureus biofilm formation and improve response to antibiotics. PLoS One, 7(1), e28737.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Rabin, N., Zheng, Y., Opoku-Temeng, C., Du, Y., Bonsu, E., & Sintim, H. O. (2015). Agents that inhibit bacterial biofilm formation. Future Medicinal Chemistry, 7(5), 647–671.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Ramasubbu, N., Thomas, L. M., Ragunath, C., & Kaplan, J. B. (2005). Structural analysis of dispersin B, a biofilm-releasing glycoside hydrolase from the periodontopathogen Actinobacillus actinomycetemcomitans. Journal of Molecular Biology, 349(3), 475–486.PubMedCrossRefPubMedCentralGoogle Scholar
  96. Reck, M., Rutz, K., Kunze, B., Tomasch, J., Surapaneni, S. K., Schulz, S., & Wagner-Dobler, I. (2011). The biofilm inhibitor carolacton disturbs membrane integrity and cell division of Streptococcus mutans through the serine/threonine protein kinase PknB. Journal of Bacteriology, 193(20), 5692–5706.PubMedPubMedCentralCrossRefGoogle Scholar
  97. Reddy, K. V., Yedery, R. D., & Aranha, C. (2004). Antimicrobial peptides: premises and promises. International Journal of Antimicrobial Agents, 24(6), 536–547.PubMedCrossRefPubMedCentralGoogle Scholar
  98. Reffuveille, F., de la Fuente-Nunez, C., Mansour, S., & Hancock, R. E. (2014). A broad-spectrum antibiofilm peptide enhances antibiotic action against bacterial biofilms. Antimicrobial Agents and Chemotherapy, 58(9), 5363–5371.PubMedPubMedCentralCrossRefGoogle Scholar
  99. Ren, D., Sims, J. J., & Wood, T. K. (2001). Inhibition of biofilm formation and swarming of Escherichia coli by (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone. Environmental Microbiology, 3(11), 731–736.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Ren, D., Sims, J. J., & Wood, T. K. (2002). Inhibition of biofilm formation and swarming of Bacillus subtilis by (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone. Letters in Applied Microbiology, 34(4), 293–299.PubMedCrossRefPubMedCentralGoogle Scholar
  101. Robijns, S. C., De Pauw, B., Loosen, B., Marchand, A., Chaltin, P., De Keersmaecker, S. C., Vanderleyden, J., & Steenackers, H. P. (2012). Identification and characterization of 4-[4-(3-phenyl-2-propen-1-yl)-1-piperazinyl]-5H-pyrimido[5,4-b]indole derivatives as Salmonella biofilm inhibitors. FEMS Immunology and Medical Microbiology, 65(2), 390–394.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Rogers, S. A., Huigens, R. W., 3rd, Cavanagh, J., & Melander, C. (2010). Synergistic effects between conventional antibiotics and 2-aminoimidazole-derived antibiofilm agents. Antimicrobial Agents and Chemotherapy, 54(5), 2112–2118.PubMedPubMedCentralCrossRefGoogle Scholar
  103. Rogers, S. A., & Melander, C. (2008). Construction and screening of a 2-aminoimidazole library identifies a small molecule capable of inhibiting and dispersing biofilms across bacterial order, class, and phylum. Angewandte Chemie International Edition, 47(28), 5229–5231.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Roy, V., Meyer, M. T., Smith, J. A., Gamby, S., Sintim, H. O., Ghodssi, R., & Bentley, W. E. (2013). AI-2 analogs and antibiotics: A synergistic approach to reduce bacterial biofilms. Applied Microbiology and Biotechnology, 97(6), 2627–2638.PubMedCrossRefPubMedCentralGoogle Scholar
  105. Rumbo-Feal, S., Gomez, M. J., Gayoso, C., Alvarez-Fraga, L., Cabral, M. P., Aransay, A. M., Rodriguez-Ezpeleta, N., Fullaondo, A., Valle, J., Tomas, M., Bou, G., & Poza, M. (2013). Whole transcriptome analysis of Acinetobacter baumannii assessed by RNA-sequencing reveals different mRNA expression profiles in biofilm compared to planktonic cells. PLoS One, 8(8), e72968.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Sambanthamoorthy, K., Gokhale, A. A., Lao, W., Parashar, V., Neiditch, M. B., Semmelhack, M. F., Lee, I., & Waters, C. M. (2011). Identification of a novel benzimidazole that inhibits bacterial biofilm formation in a broad-spectrum manner. Antimicrobial Agents and Chemotherapy, 55(9), 4369–4378.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Sambanthamoorthy, K., Sloup, R. E., Parashar, V., Smith, J. M., Kim, E. E., Semmelhack, M. F., Neiditch, M. B., & Waters, C. M. (2012). Identification of small molecules that antagonize diguanylate cyclase enzymes to inhibit biofilm formation. Antimicrobial Agents and Chemotherapy, 56(10), 5202–5211.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Savage, V. J., Chopra, I., & O’Neill, A. J. (2013). Staphylococcus aureus biofilms promote horizontal transfer of antibiotic resistance. Antimicrobial Agents and Chemotherapy, 57(4), 1968–1970.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Selan, L., Berlutti, F., Passariello, C., Comodi-Ballanti, M. R., & Thaller, M. C. (1993). Proteolytic enzymes: A new treatment strategy for prosthetic infections? Antimicrobial Agents and Chemotherapy, 37(12), 2618–2621.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Simonetti, O., Cirioni, O., Mocchegiani, F., Cacciatore, I., Silvestri, C., Baldassarre, L., Orlando, F., Castelli, P., Provinciali, M., Vivarelli, M., Fornasari, E., Giacometti, A., & Offidani, A. (2013). The efficacy of the quorum sensing inhibitor FS8 and tigecycline in preventing prosthesis biofilm in an animal model of staphylococcal infection. International Journal of Molecular Sciences, 14(8), 16321–16332.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Singh, S., Kalia, N. P., Joshi, P., Kumar, A., Sharma, P. R., Kumar, A., Bharate, S. B., & Khan, I. A. (2017). Boeravinone B, a novel dual inhibitor of NorA bacterial efflux pump of Staphylococcus aureus and human P-glycoprotein, reduces the biofilm formation and intracellular invasion of Bacteria. Frontiers in Microbiology, 8, 1868.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Slachmuylders, L., Van Acker, H., Brackman, G., Sass, A., Van Nieuwerburgh, F., & Coenye, T. (2018). Elucidation of the mechanism behind the potentiating activity of baicalin against Burkholderia cenocepacia biofilms. PLoS One, 13(1), e0190533.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Smith, K., & Hunter, I. S. (2008). Efficacy of common hospital biocides with biofilms of multi-drug resistant clinical isolates. Journal of Medical Microbiology, 57(Pt 8), 966–973.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Stacy, D. M., Welsh, M. A., Rather, P. N., & Blackwell, H. E. (2012). Attenuation of quorum sensing in the pathogen Acinetobacter baumannii using non-native N-acyl homoserine lactones. ACS Chemical Biology, 7(10), 1719–1728.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Stalder, T., & Top, E. (2016). Plasmid transfer in biofilms: A perspective on limitations and opportunities. NPJ Biofilms Microbiomes, 2, 16022.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Stewart, P. S., & Costerton, J. W. (2001). Antibiotic resistance of bacteria in biofilms. Lancet, 358(9276), 135–138.PubMedCrossRefGoogle Scholar
  117. Stoodley, P., Sauer, K., Davies, D. G., & Costerton, J. W. (2002). Biofilms as complex differentiated communities. Annual Review of Microbiology, 56, 187–209.PubMedCrossRefPubMedCentralGoogle Scholar
  118. Su, S., Panmanee, W., Wilson, J. J., Mahtani, H. K., Li, Q., Vanderwielen, B. D., Makris, T. M., Rogers, M., McDaniel, C., Lipscomb, J. D., Irvin, R. T., Schurr, M. J., Lancaster, J. R., Jr., Kovall, R. A., & Hassett, D. J. (2014). Catalase (KatA) plays a role in protection against anaerobic nitric oxide in Pseudomonas aeruginosa. PLoS One, 9(3), e91813.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Sutherland, I. (2001). Biofilm exopolysaccharides: A strong and sticky framework. Microbiology, 147(Pt 1), 3–9.PubMedCrossRefPubMedCentralGoogle Scholar
  120. Tetz, V. V., & Tetz, G. V. (2010). Effect of extracellular DNA destruction by DNase I on characteristics of forming biofilms. DNA and Cell Biology, 29(8), 399–405.PubMedCrossRefPubMedCentralGoogle Scholar
  121. Thompson, R. J., Bobay, B. G., Stowe, S. D., Olson, A. L., Peng, L., Su, Z., Actis, L. A., Melander, C., & Cavanagh, J. (2012). Identification of BfmR, a response regulator involved in biofilm development, as a target for a 2-Aminoimidazole-based antibiofilm agent. Biochemistry, 51(49), 9776–9778.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Tomaras, A. P., Flagler, M. J., Dorsey, C. W., Gaddy, J. A., & Actis, L. A. (2008). Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology-Sgm, 154, 3398–3409.CrossRefGoogle Scholar
  123. Traxler, M. F., Summers, S. M., Nguyen, H. T., Zacharia, V. M., Hightower, G. A., Smith, J. T., & Conway, T. (2008). The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli. Molecular Microbiology, 68(5), 1128–1148.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Tsuchikama, K., Zhu, J., Lowery, C. A., Kaufmann, G. F., & Janda, K. D. (2012). C4-alkoxy-HPD: A potent class of synthetic modulators surpassing nature in AI-2 quorum sensing. Journal of the American Chemical Society, 134(33), 13562–13564.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Tuomanen, E., Durack, D. T., & Tomasz, A. (1986). Antibiotic tolerance among clinical isolates of bacteria. Antimicrobial Agents and Chemotherapy, 30(4), 521–527.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Van Acker, H., & Coenye, T. (2016). The role of efflux and physiological adaptation in biofilm tolerance and resistance. The Journal of Biological Chemistry, 291(24), 12565–12572.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Van Acker, H., Van Dijck, P., & Coenye, T. (2014). Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. Trends in Microbiology, 22(6), 326–333.PubMedCrossRefPubMedCentralGoogle Scholar
  128. Vendeville, A., Winzer, K., Heurlier, K., Tang, C. M., & Hardie, K. R. (2005). Making ‘sense’ of metabolism: Autoinducer-2, LuxS and pathogenic bacteria. Nature Reviews. Microbiology, 3(5), 383–396.PubMedCrossRefPubMedCentralGoogle Scholar
  129. Webb, J. S., Givskov, M., & Kjelleberg, S. (2003). Bacterial biofilms: Prokaryotic adventures in multicellularity. Current Opinion in Microbiology, 6(6), 578–585.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Wood, T. K., Knabel, S. J., & Kwan, B. W. (2013). Bacterial persister cell formation and dormancy. Applied and Environmental Microbiology, 79(23), 7116–7121.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Wood, T. K., Lee, J., Zhang, X. S., Hegde, M., Bentley, W. E., & Jayaraman, A. (2008). Indole cell signaling occurs primarily at low temperatures in Escherichia coli. ISME Journal, 2(10), 1007–1023.PubMedCrossRefPubMedCentralGoogle Scholar
  132. Worthington, R. J., Blackledge, M. S., & Melander, C. (2013). Small-molecule inhibition of bacterial two-component systems to combat antibiotic resistance and virulence. Future Medicinal Chemistry, 5(11), 1265–1284.PubMedCrossRefPubMedCentralGoogle Scholar
  133. Worthington, R. J., Richards, J. J., & Melander, C. (2012). Small molecule control of bacterial biofilms. Organic & Biomolecular Chemistry, 10(37), 7457–7474.CrossRefGoogle Scholar
  134. Wright, C. J., Wu, H., Melander, R. J., Melander, C., & Lamont, J. (2014). Disruption of heterotypic community development by Porphyromonas gingivalis with small molecule inhibitors. Molecular Oral Microbiology, 29(5), 185–193.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Wu, H., Moser, C., Wang, H. Z., Hoiby, N., & Song, Z. J. (2015). Strategies for combating bacterial biofilm infections. International Journal of Oral Science, 7(1), 1–7.PubMedCrossRefPubMedCentralGoogle Scholar
  136. Yan, H., & Chen, W. (2010). 3′,5′-cyclic diguanylic acid: A small nucleotide that makes big impacts. Chemical Society Reviews, 39(8), 2914–2924.PubMedCrossRefPubMedCentralGoogle Scholar
  137. Yarwood, J. M., Bartels, D. J., Volper, E. M., & Greenberg, E. P. (2004). Quorum sensing in Staphylococcus aureus biofilms. Journal of Bacteriology, 186(6), 1838–1850.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Yates, E. A., Philipp, B., Buckley, C., Atkinson, S., Chhabra, S. R., Sockett, R. E., Goldner, M., Dessaux, Y., Camara, M., Smith, H., & Williams, P. (2002). N-acylhomoserine lactones undergo lactonolysis in a pH-, temperature-, and acyl chain length-dependent manner during growth of Yersinia pseudotuberculosis and Pseudomonas aeruginosa. Infection and Immunity, 70(10), 5635–5646.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of Notre DameNotre DameUSA

Personalised recommendations