Actinobacteria—a promising natural source of anti-biofilm agents

  • Adzzie-Shazleen AzmanEmail author
  • Christina-Injan Mawang
  • Jasmine-Elanie Khairat
  • Sazaly AbuBakarEmail author


A biofilm is a community of microorganisms attached to a surface and embedded in a matrix of extracellular polymeric substances. Biofilms confer resistance towards conventional antibiotic treatments; thus, there is an urgent need for newer and more effective antimicrobial agents that can act against these biofilms. Due to this situation, various studies have been done to investigate the anti-biofilm effects of natural products including bioactive compounds extracted from microorganisms such as Actinobacteria. This review provides an insight into the anti-biofilm potential of Actinobacteria against various pathogenic bacteria, which hopefully provides useful information, guidance, and improvements for future antimicrobial studies. Nevertheless, further research on the anti-biofilm mechanisms and compound modifications to produce more potent anti-biofilm effects are required.


Streptomyces Non-Streptomyces Actinobacteria Anti-biofilm Biofilms 



This work was supported by the grant from Yayasan Pahang (GA004-2018) awarded to Dr. Adzzie Shazleen Azman.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. Abd-Elanby H, Abo-Elala G, Abdel-Raouf U, Abd-Elwahab A, Hamed M (2016) Antibacterial and anticancer activity of marine Streptomyces parvus: optimization and application. Biotechnol Biotechnol Equip 30:1CrossRefGoogle Scholar
  2. Abu Sayem SM, Manzo E, Ciavatta L, Tramice A, Cordone A, Zanfardino A, De Felice M, Varcamonti M (2011) Anti-biofilm activity of an exopolysaccharide from a sponge-associated strain of Bacillus licheniformis. Microb Cell Factories 10:74CrossRefGoogle Scholar
  3. Agarwal A, Singh KP, Jain A (2010) Medical significance and management of staphylococcal biofilm. FEMS Immunol Med Microbiol 58:147–160CrossRefGoogle Scholar
  4. Alihosseini F, Ju KS, Lango J, Hammock BD, Sun G (2008) Antibacterial colorants: characterization of prodiginines and their applications on textile materials. Biotechnol Prog 24:742–747CrossRefGoogle Scholar
  5. Augustine N, Wilson PA, Kerkar S, Thomas S (2012) Arctic actinomycetes as potential inhibitors of Vibrio cholerae biofilm. Curr Microbiol 64:338–342CrossRefGoogle Scholar
  6. Azman AS, Othman I, Fang CM, Chan KG, Goh BH, Lee LH (2017) Antibacterial, anticancer and neuroprotective activities of rare actinobacteria from mangrove forest soils. Indian J Microbiol 57:177–187CrossRefGoogle Scholar
  7. Bakkiyaraj D, Pandian S (2010) In-vitro and in-vivo antibiofilm activity of a coral associated actinomycete against drug resistant Staphylococcus aureus biofilms. Biofouling 26:711–717CrossRefGoogle Scholar
  8. Balasubramanian S, Othman EM, Kampik D, Stopper H, Hentschel U, Ziebuhr W, Oelschlaeger TA, Abdelmohsen UR (2017) Marine sponge-derived Streptomyces sp. SBT343 extract inhibits staphylococcal biofilm formation. Front Microbiol 8:236CrossRefGoogle Scholar
  9. Banat IM, Diaz De Rienzo MA, Quinn GA (2014) Microbial biofilms: biosurfactants as antibiofilm agents. Appl Microbiol Biotechnol 98:9915–9929CrossRefGoogle Scholar
  10. Barka EA, Vatsa P, Sanchez L, Gaveau-Vaillant N, Jacquard C, Klenk HP, Clément C, Ouhdouch Y, van Wezel GP (2016) Taxonomy, physiology, and natural products of Actinobacteria. Microbiol Mol Biol Rev 80:1–43CrossRefGoogle Scholar
  11. Berdy J (2012) Thought and facts about antibiotic: where we are now and where we are heading. J Antibiot 65:385–395CrossRefGoogle Scholar
  12. Berne C, Kysela DT, Brun YV (2011) A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm. Mol Microbiol 77(4):815–829Google Scholar
  13. Bottone EJ (2010) Bacillus cereus, a volatile human pathogen. Clin Microbiol Rev 23(2):382–398CrossRefGoogle Scholar
  14. Camins BC (2013) Prevention and treatment of hemodialysis-related bloodstream infections. Semin Dial 26:476–481CrossRefGoogle Scholar
  15. Chenoweth C, Saint S (2013) Preventing catheter-associated urinary tract infections in the intensive care unit. Crit Care Clin 29:19–32CrossRefGoogle Scholar
  16. Claverías FP, Undabarrena A, Gonzalez M, Seeger M, Camara B (2015) Culturable diversity and antimicrobial activity of Actinobacteria from marine sediments in Valparaiso bay, Chile. Front Microbiol 6:1–11CrossRefGoogle Scholar
  17. Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830(6):3670–3695CrossRefGoogle Scholar
  18. Dang H, Lovell CR (2016) Microbial surface colonization and biofilm development in marine environments. Microbiol Mol Biol Rev 80:91–138CrossRefGoogle Scholar
  19. Dufour D, Leung V, Lévesque CM (2010) Bacterial biofilm: structure, function, and antimicrobial resistance. Endod Top 22(1):2–16CrossRefGoogle Scholar
  20. Flemming HC, Wingender J (2010) The biofilm matrix. Nat Rev Microbiol 8:623–633CrossRefGoogle Scholar
  21. Francolini I, Donelli G (2010) Prevention and control of biofilm-based medical-device-related infections. FEMS Immunol Med Microbiol 59:227–238CrossRefGoogle Scholar
  22. Hall CW, Mah TF (2017) Molecular mechanisms of biofilm-bsed antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev 41(3):276–301CrossRefGoogle Scholar
  23. Hengzhuang W, Wu H, Ciofu O, Song Z, Hǿiby N (2011) Pharmacokinetics/pharmacodynamics of colistin and imipenem on mucoid and nonmucoid Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 55:4469–4474CrossRefGoogle Scholar
  24. Hengzhuang W, Wu H, Ciofu O, Song Z, Hǿiby N (2012) In vivo pharmacokinetics/pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection. Antimicrob Agents Chemother 56(5):2683–2690CrossRefGoogle Scholar
  25. Hennig S, Wai SN, Ziebuhr W (2007) Spontaneous switch to PIA-independent biofilm formation in an Ica-positive Staphylococcus epidermidis isolate. Int J Med Microbiol 297:117–122CrossRefGoogle Scholar
  26. Hibbing ME, Fuqua C, Parsek MR, Peterson SB (2010) Bacterial competition: surviving and thriving in the microbial jungle. Nat Rev Microbiol 8:15–25CrossRefGoogle Scholar
  27. Ikuma K, Decho AW, Lau BLT (2013) The extracellular bastions of bacteria—a biofilm way of life. Nat Edu Knowledge 4:2Google Scholar
  28. Kim YG, Lee JH, Kim CJ, Lee JC, Ju YJ, Cho MH, Lee J (2012) Antibiofilm activity of Streptomyces sp. BF230 and Kribbella sp. 1562 against Pseudomonas aeruginosa. Appl Microbiol Biotechnol 96:1607–1617CrossRefGoogle Scholar
  29. Lazâr V, Chifiriuc MC (2010) Medical significance and new therapeutical strategies for biofilm associated infections. Roum Arch Microbiol Immunol 69:125–138PubMedGoogle Scholar
  30. Lee JH, Kim YG, Kim CJ, Lee JC, Cho MH, Lee J (2012) Indole-3-acetaldehyde from Rhodococcus sp. BFI 332 inhibits Escherichia coli O157:H7 biofilm formation. Appl Microbiol Biotechnol 96:1071–1078CrossRefGoogle Scholar
  31. Leroy C, Delbarre-Ladrat C, Ghillebaert F, Compere C, Combes D (2008) Effects of commercial enzymes on the adhesion of a marine biofilm-forming bacterium. Biofouling. 24:11–22CrossRefGoogle Scholar
  32. Limoli DH, Jones CJ, Wozniak DJ (2015) Bacterial extracellular polysaccharides in biofilm formation and function. Microbiol Spectr 3(3).
  33. Majed R, Faille C, Kallassy M, Gohar M (2016) Bacillus cereus biofilms—same, only different. Front Microbiol 7:1054–1054CrossRefGoogle Scholar
  34. Mohammadipanah F, Wink J (2015) Actinobacteria from arid and desert habitats: diversity and biological activity. Front Microbiol 6:1541PubMedGoogle Scholar
  35. Nadell CD, Xavier JB, Foster KR (2009) The sociobiology of biofilms. FEMS Microbiol Rev 33:206–224CrossRefGoogle Scholar
  36. O'Toole G, Kaplan HB, Kolter R (2000) Biofilm formation as microbial development. Annu Rev Microbiol 54:49–79CrossRefGoogle Scholar
  37. Papireddy K, Smilkstein M, Kelly JX, Shweta SSM, Alhamadsheh M, Haynes SW, Challis GL, Reynolds KS (2011) Antimalarial activity of natural and synthetic prodiginines. J Med Chem 11:5296–5306CrossRefGoogle Scholar
  38. Park JH, Lee JH, Kim CJ, Lee JC, Cho MH, Lee J (2012) Extracellular protease in actinomycetes culture supernatants inhibits and detaches Staphylococcus aureus biofilm formation. Biotechnol Lett 34:655–661CrossRefGoogle Scholar
  39. Park SR, Tripathi A, Wu J, Schultz PJ, Yim I, McQuade TJ, Yu F, Arevang CJ, Mensah AY, Giselle TC et al (2016) Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway. Nat Commun 7:10710CrossRefGoogle Scholar
  40. Penesyan A, Gillings M, Paulsen IT (2015) Antibiotic discovery: combating bacterial resistance in cells and in biofilm communities. Molecules. 20(4):5286–5298CrossRefGoogle Scholar
  41. Raveh A, Delekta PC, Dobry CJ, Peng W, Schultz PJ, Blakely PK, Tai AW, Matainaho T, Irani DN, Sherman DH, Miller DJ (2013) Discovery of potent broad spectrum antivirals derived from marine actinobacteria. PLoS One 8:e82318CrossRefGoogle Scholar
  42. Rendueles O, Kaplan JB, Ghigo JM (2012) Antibiofilm polysaccharides. Environ Microbiol 15(2):334–346CrossRefGoogle Scholar
  43. Rodrigues LR (2011) Inhibition of bacterial adhesion on medical devices. Adv Exp Med Biol 715:351–367CrossRefGoogle Scholar
  44. Roy R, Tiwari M, Donelli G, Tiwari V (2018) Strategies for combating bacterial biofilms: a focus on anti-biofilm agents and their mechanisms of action. Virulence. 9:522–554CrossRefGoogle Scholar
  45. Saleem HG, Aftab U, Sajid I, Abbas Z, Sabri AN (2015) Effect of crude extracts of selected actinomycetes on biofilm formation of A. schindleri, M. aci, and B. cereus. J Basic Microbiol 55:645–651CrossRefGoogle Scholar
  46. Schallenberger MA, Niessen S, Shao CX, Fowler BJ, Romesberg FE (2012) Type 1 signal peptidase and protein secretion in Staphylococcus aureus. J Bacteriol 194:2677–2686CrossRefGoogle Scholar
  47. Simoes M (2011) Antimicrobial strategies effective against infectious bacterial biofilms. Curr Med Chem 18:2129–2145CrossRefGoogle Scholar
  48. Spadari C, Antunes T, Teixeira R, Minotto E, Fuentefria AM, Van der Sand S (2015) Antifungal activity of actinobacteria against fungus isolates of clinical importance. Brazilian J Biol Sci 11:439–443Google Scholar
  49. Stubbendieck RM, Vargas-Bautista C, Straight PD (2016) Bacterial communities: interactions to scale. Front Microbiol 7:1234CrossRefGoogle Scholar
  50. Suzuki N, Ohtaguro N, Yoshida Y, Hirai M, Matsuo H, Yamada Y, Imamura N, Tsuchiya T (2015) A compound inhibits biofilm formation of Staphylococcus aureus from Streptomyces. Biol Pharm Bull 38:889–892CrossRefGoogle Scholar
  51. Thenmozhi R, Nithyanand P, Rathna J, Pandian SK (2009) Antibiofilm activity of coral-associated bacteria against different clinical M serotypes of Streptococcus pyogenes. FEMS Immu Med Microbiol 57:284–294CrossRefGoogle Scholar
  52. Uhlich GA, Cooke PH, Solomon EB (2006) Analyses of the red-dry-rough phenotype of an Escherichia coli O157:H7 strain and its role in biofilm formation and resistance to antibacterial agents. Appl Environ Microbiol 72:2564–2572CrossRefGoogle Scholar
  53. Waturangi DE, Rahayu BS, Lalu KY, Mulyono N (2016) Characterization of bioactive compound from actinomycetes for antibiofilm activity against Gram-negative and Gram-positive bacteria. Malaysian J Microbiol 12:291–299Google Scholar
  54. You J, Xue X, Cao L, Lu X, Wang J, Zhang L, Zhou S (2007) Inhibition of Vibrio biofilm formation by a marine actinomycete strain A66. Appl Microbiol Biotechnol 76:1137–1144CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Tropical Infectious Diseases Research and Education Centre, Department of Medical Microbiology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  2. 2.School of ScienceMonash University MalaysiaBandar SunwayMalaysia
  3. 3.Institute of Biological Sciences, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  4. 4.Department of Medical Microbiology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia

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