Indian Journal of Microbiology

, Volume 59, Issue 1, pp 3–12 | Cite as

Biofilms: Architecture, Resistance, Quorum Sensing and Control Mechanisms

  • Priti SaxenaEmail author
  • Yogesh Joshi
  • Kartik Rawat
  • Renu Bisht
Review Article


Biofilm is a mode of living employed by many pathogenic and environmental microbes to proliferate as multicellular aggregates on inert inanimate or biological substrates. Several microbial diseases are associated with biofilms that pose challenges in treatment with antibiotics targeting individual cells. Bacteria in biofilms secrete exopolymeric substances that contribute to architectural stability and provide a secure niche to inhabiting cells. Quorum sensing (QS) plays essential roles in biofilm development. Pathogenic bacteria in biofilms utilize QS mechanisms to activate virulence and develop antibiotic resistance. This review is a brief overview of biofilm research and provides updates on recent understandings on biofilm development, antibiotic resistance and transmission, and importance of QS mechanisms. Strategies to combat biofilm associated diseases including anti-biofilm substances, quorum quenching molecules, bio-surfactants and competitive inhibitors are briefly discussed. The review concludes with updates on recent approaches utilized for biofilm inhibition and provides perspectives for further research in the field.


Biofilms eDNA Antibiotic resistance Quorum sensing Quorum quenching 



PS gratefully acknowledges Innovative Young Biotechnologist Award (IYBA) of Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India and South Asian University (SAU) Startup Research Grant, SAU, India for providing funds and support for this study.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Algburi A, Comito N, Kashtanov D, Dicks LM, Chikindas ML (2016) Control of biofilm formation: antibiotics and beyond. Appl Environ Microbiol. Google Scholar
  2. 2.
    Jamal M, Ahmad W, Andleeb S, Jalil F, Imran M, Nawaz MA, Hussain T, Ali M, Rafiq M, Kamil MA (2018) Bacterial biofilm and associated infections. J Chin Med Assoc 81:7–11. CrossRefGoogle Scholar
  3. 3.
    Wu H, Moser C, Wang H-Z, Høiby N, Song Z-J (2015) Strategies for combating bacterial biofilm infections. Int J Oral Sci 7:1. CrossRefGoogle Scholar
  4. 4.
    Miquel S, Lagrafeuille R, Souweine B, Forestier C (2016) Anti-biofilm activity as a health issue. Front Microbiol 7:592. CrossRefGoogle Scholar
  5. 5.
    Balcázar JL, Subirats J, Borrego CM (2015) The role of biofilms as environmental reservoirs of antibiotic resistance. Front Microbiol 6:1216. CrossRefGoogle Scholar
  6. 6.
    Kanwar I, Sah AK, Suresh PK (2017) Biofilm-mediated antibiotic-resistant oral bacterial infections: mechanism and combat strategies. Curr Pharm Des 23:2084–2095. CrossRefGoogle Scholar
  7. 7.
    Hall CW, Mah T-F (2017) Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev 41:276–301. CrossRefGoogle Scholar
  8. 8.
    Singh S, Singh SK, Chowdhury I, Singh R (2017) Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents. Open Microbiol J 11:53. CrossRefGoogle Scholar
  9. 9.
    Roilides E, Simitsopoulou M, Katragkou A, Walsh TJ (2015) How biofilms evade host defenses. Microbiol Spectr. Google Scholar
  10. 10.
    Stalder T, Top E (2016) Plasmid transfer in biofilms: a perspective on limitations and opportunities. NPJ Biofilms Microbiomes 2:16022. CrossRefGoogle Scholar
  11. 11.
    Kouzel N, Oldewurtel ER, Maier B (2015) Gene transfer efficiency in gonococcal biofilms: role of biofilm age, architecture, and pilin antigenic variation. J Bacteriol 197:2422–2431. CrossRefGoogle Scholar
  12. 12.
    Smolentseva O, Gusarov I, Gautier L, Shamovsky I, DeFrancesco AS, Losick R, Nudler E (2017) Mechanism of biofilm-mediated stress resistance and lifespan extension in C. elegans. Sci Rep 7:7137. CrossRefGoogle Scholar
  13. 13.
    Chen XP, Ali L, Wu L-Y, Liu C, Gang CX, Huang QF, Ruan JH, Bao SY, Rao YP, Yu D (2018) Biofilm formation plays a role in the formation of multidrug-resistant Escherichia coli toward nutrients in microcosm experiments. Front Microbiol 9:367. CrossRefGoogle Scholar
  14. 14.
    Kalia VC (2013) Quorum sensing inhibitors: an overview. Biotechnol Adv 31:224–245. CrossRefGoogle Scholar
  15. 15.
    Kostakioti M, Hadjifrangiskou M, Hultgren SJ (2013) Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med 3:a010306. CrossRefGoogle Scholar
  16. 16.
    Flemming H-C, Wingender J, Szewzyk U, Steinberg P, Rice SA, Kjelleberg S (2016) Biofilms: an emergent form of bacterial life. Nat Rev Microbiol 14:563. CrossRefGoogle Scholar
  17. 17.
    Kumar A, Alam A, Rani M, Ehtesham NZ, Hasnain SE (2017) Biofilms: survival and defense strategy for pathogens. Int J Med Microbiol. Google Scholar
  18. 18.
    Azeredo J, Azevedo NF, Briandet R, Cerca N, Coenye T, Costa AR, Desvaux M, Di Bonaventura G, Hébraud M, Jaglic Z, Kačániová M, Knøchel S, Lourenço A, Mergulhão F, Meyer RL, Nychas G, Simões M, Tresse O, Sternberg C (2017) Critical review on biofilm methods. Crit Rev Microbiol 43:313–351. CrossRefGoogle Scholar
  19. 19.
    Satpathy S, Sen SK, Pattanaik S, Raut S (2016) Review on bacterial biofilm: an universal cause of contamination. Biocatal Agric Biotechnol 7:56–66. CrossRefGoogle Scholar
  20. 20.
    Gupta P, Sarkar S, Das B, Bhattacharjee S, Tribedi P (2016) Biofilm, pathogenesis and prevention—a journey to break the wall: a review. Arch Microbiol 198:1–15. CrossRefGoogle Scholar
  21. 21.
    Limoli DH, Jones CJ, Wozniak DJ (2015) Bacterial extracellular polysaccharides in biofilm formation and function. Microbiol Spectr. Google Scholar
  22. 22.
    Hobley L, Harkins C, MacPhee CE, Stanley-Wall NR (2015) Giving structure to the biofilm matrix: an overview of individual strategies and emerging common themes. FEMS Microbiol Rev 39:649–669. CrossRefGoogle Scholar
  23. 23.
    Smith DR, Price JE, Burby PE, Blanco LP, Chamberlain J, Chapman MR (2017) The production of Curli amyloid fibers is deeply integrated into the biology of Escherichia coli. Biomolecules 7:75. CrossRefGoogle Scholar
  24. 24.
    Diehl A, Roske Y, Ball L, Chowdhury A, Hiller M, Molière N, Kramer R, Stöppler D, Worth CL, Schlegel B, Leidert M, Cremer N, Erdmann N, Lopez D, Stephanowitz H, Krause E, van Rossum BJ, Schmieder P, Heinemann U, Turgay K, Akbey Ü, Oschkinat H (2018) Structural changes of TasA in biofilm formation of Bacillus subtilis. Proc Natl Acad Sci USA 115:3237–3242. CrossRefGoogle Scholar
  25. 25.
    Donlan RM (2002) Biofilms: microbial life on surfaces. Emerg Infect Dis 8:881. CrossRefGoogle Scholar
  26. 26.
    Díaz-Salazar C, Calero P, Espinosa-Portero R, Jiménez-Fernández A, Wirebrand L, Velasco-Domínguez MG, López-Sánchez A, Shingler V, Govantes F (2017) The stringent response promotes biofilm dispersal in Pseudomonas putida. Sci Rep 7:18055. CrossRefGoogle Scholar
  27. 27.
    Fleming D, Rumbaugh KP (2017) Approaches to dispersing medical biofilms. Microorganisms 5:15. CrossRefGoogle Scholar
  28. 28.
    Zhao X, Zhao F, Wang J, Zhong N (2017) Biofilm formation and control strategies of foodborne pathogens: food safety perspectives. RSC Adv 7:36670–36683. CrossRefGoogle Scholar
  29. 29.
    Han Q, Song X, Zhang Z, Fu J, Wang X, Malakar PK, Liu H, Pan Y, Zhao Y (2017) Removal of foodborne pathogen biofilms by acidic electrolyzed water. Front Microbiol 8:988. CrossRefGoogle Scholar
  30. 30.
    Li Y-H, Tian X (2012) Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel) 12:2519–2538. CrossRefGoogle Scholar
  31. 31.
    Whiteley M, Diggle SP, Greenberg EP (2017) Progress in and promise of bacterial quorum sensing research. Nature 551:313. CrossRefGoogle Scholar
  32. 32.
    Basavaraju M, Sisnity VS, Palaparthy R, Addanki PK (2016) Quorum quenching: signal jamming in dental plaque biofilms. J Dent Sci 11:349–352. CrossRefGoogle Scholar
  33. 33.
    Voběrková S, Hermanová S, Hrubanová K, Krzyžánek V (2016) Biofilm formation and extracellular polymeric substances (EPS) production by Bacillus subtilis depending on nutritional conditions in the presence of polyester film. Folia Microbiol (Praha) 61:91–100. CrossRefGoogle Scholar
  34. 34.
    Inaba T, Hori T, Aizawa H, Ogata A, Habe H (2017) Architecture, component, and microbiome of biofilm involved in the fouling of membrane bioreactors. NPJ Biofilms Microbiomes 3:5. CrossRefGoogle Scholar
  35. 35.
    Kundukad B, Schussman M, Yang K, Seviour T, Yang L, Rice SA, Kjelleberg S, Doyle PS (2017) Mechanistic action of weak acid drugs on biofilms. Sci Rep 7:4783. CrossRefGoogle Scholar
  36. 36.
    Xiao J, Hara AT, Kim D, Zero DT, Koo H, Hwang G (2017) Biofilm three-dimensional architecture influences in situ pH distribution pattern on the human enamel surface. Int J Oral Sci 9:74. CrossRefGoogle Scholar
  37. 37.
    O’Leary D, McCabe EM, McCusker MP, Martins M, Fanning S, Duffy G (2015) Acid environments affect biofilm formation and gene expression in isolates of Salmonella enterica Typhimurium DT104. Int J Food Microbiol 206:7–16. CrossRefGoogle Scholar
  38. 38.
    Berlanga M, Guerrero R (2016) Living together in biofilms: the microbial cell factory and its biotechnological implications. Microb Cell Fact 15:165. CrossRefGoogle Scholar
  39. 39.
    Van Acker H, Van Dijck P, Coenye T (2014) Molecular mechanisms of antimicrobial tolerance and resistance in bacterial and fungal biofilms. Trends Microbiol 22:326–333. CrossRefGoogle Scholar
  40. 40.
    Flemming H-C (2016) EPS—then and now. Microorganisms 4:41. CrossRefGoogle Scholar
  41. 41.
    Høiby N (2017) A short history of microbial biofilms and biofilm infections. APMIS 125:272–275. CrossRefGoogle Scholar
  42. 42.
    Goltermann L, Tolker-Nielsen T (2017) Importance of the exopolysaccharide matrix in antimicrobial tolerance of Pseudomonas aeruginosa aggregates. Antimicrob Agents Chemother 61:e02696. CrossRefGoogle Scholar
  43. 43.
    de Aldecoa ALI, Zafra O, González-Pastor JE (2017) Mechanisms and regulation of extracellular DNA release and its biological roles in microbial communities. Front Microbiol 8:1390. CrossRefGoogle Scholar
  44. 44.
    Das T, Sehar S, Manefield M (2013) The roles of extracellular DNA in the structural integrity of extracellular polymeric substance and bacterial biofilm development. Environ Microbiol Rep 5:778–786. CrossRefGoogle Scholar
  45. 45.
    Jung C-J, Hsu R-B, Shun C-T, Hsu C-C, Chia J-S (2017) AtlA mediates extracellular DNA release, which contributes to Streptococcus mutans biofilm formation in an experimental rat model of infective endocarditis. Infect Immun 85:e00252. CrossRefGoogle Scholar
  46. 46.
    DeFrancesco AS, Masloboeva N, Syed AK, DeLoughery A, Bradshaw N, Li G-W, Gilmore MS, Walker S, Losick R (2017) Genome-wide screen for genes involved in eDNA release during biofilm formation by Staphylococcus aureus. Proc Natl Acad Sci USA 114:E5969–E5978. CrossRefGoogle Scholar
  47. 47.
    Sena-Vélez M, Redondo C, Graham JH, Cubero J (2016) Presence of extracellular DNA during biofilm formation by Xanthomonas citri subsp. citri strains with different host range. PLoS ONE 11:e0156695. CrossRefGoogle Scholar
  48. 48.
    Okshevsky M, Meyer RL (2015) The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Crit Rev Microbiol 41:341–352. CrossRefGoogle Scholar
  49. 49.
    Koul S, Prakash J, Mishra A, Kalia VC (2016) Potential emergence of multi-quorum sensing inhibitor resistant (MQSIR) bacteria. Indian J Microbiol 56:1–18. CrossRefGoogle Scholar
  50. 50.
    Kalia V (2014) Microbes, antimicrobials and resistance: the battle goes on. Indian J Microbiol. Google Scholar
  51. 51.
    Passos da Silva D, Schofield MC, Parsek MR, Tseng BS (2017) An update on the sociomicrobiology of quorum sensing in gram-negative biofilm development. Pathogens 6:51. CrossRefGoogle Scholar
  52. 52.
    Rutherford ST, Bassler BL (2012) Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2:a012427. CrossRefGoogle Scholar
  53. 53.
    Kalia VC, Wood TK, Kumar P (2014) Evolution of resistance to quorum-sensing inhibitors. Microb Ecol 68:13–23. CrossRefGoogle Scholar
  54. 54.
    Madec E, Laszkiewicz A, Iwanicki A, Obuchowski M, Séror S (2002) Characterization of a membrane-linked Ser/Thr protein kinase in Bacillus subtilis, implicated in developmental processes. Mol Microbiol 46:571–586. CrossRefGoogle Scholar
  55. 55.
    Arora G, Sajid A, Virmani R, Singhal A, Kumar CS, Dhasmana N, Khanna T, Maji A, Misra R, Molle V, Becher D, Gerth U, Mande SC, Singh Y (2017) Ser/Thr protein kinase PrkC-mediated regulation of GroEL is critical for biofilm formation in Bacillus anthracis. NPJ Biofilms Microbiomes 3:7. CrossRefGoogle Scholar
  56. 56.
    Cluzel M-E, Zanella-Cléon I, Cozzone AJ, Fütterer K, Duclos B, Molle V (2010) The Staphylococcus aureus autoinducer-2 synthase LuxS is regulated by Ser/Thr phosphorylation. J Bacteriol 192:6295–6301. CrossRefGoogle Scholar
  57. 57.
    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 9:522–554. CrossRefGoogle Scholar
  58. 58.
    Abraham W-R (2016) Going beyond the control of quorum-sensing to combat biofilm infections. Antibiotics (Basel) 5:3. CrossRefGoogle Scholar
  59. 59.
    Kalia VC, Purohit HJ (2011) Quenching the quorum sensing system: potential antibacterial drug targets. Crit Rev Microbiol 37:121–140. CrossRefGoogle Scholar
  60. 60.
    Kumar P, Patel SK, Lee J-K, Kalia VC (2013) Extending the limits of Bacillus for novel biotechnological applications. Biotechnol Adv 31:1543–1561. CrossRefGoogle Scholar
  61. 61.
    Kalia VC, Raju SC, Purohit HJ (2011) Genomic analysis reveals versatile organisms for quorum quenching enzymes: acyl-homoserine lactone-acylase and-lactonase. Open Microbiol J 5:1. CrossRefGoogle Scholar
  62. 62.
    Koul S, Kalia VC (2017) Multiplicity of quorum quenching enzymes: a potential mechanism to limit quorum sensing bacterial population. Indian J Microbiol 57:100–108. CrossRefGoogle Scholar
  63. 63.
    Huma N, Shankar P, Kushwah J, Bhushan A, Joshi J, Mukherjee T, Raju SC, Purohit HJ, Kalia VC (2011) Diversity and polymorphism in AHL-lactonase gene (aiiA) of Bacillus. J Microbiol Biotechnol 21:1001–1011. CrossRefGoogle Scholar
  64. 64.
    Grandclément C, Tannières M, Moréra S, Dessaux Y, Faure D (2015) Quorum quenching: role in nature and applied developments. FEMS Microbiol Rev 40:86–116. CrossRefGoogle Scholar
  65. 65.
    Rabin N, Zheng Y, Opoku-Temeng C, Du Y, Bonsu E, Sintim HO (2015) Agents that inhibit bacterial biofilm formation. Future Med Chem 7:647–671. CrossRefGoogle Scholar
  66. 66.
    Kalia VC, Kumar P, Pandian ST, Sharma P (2015) Biofouling control by quorum quenching. In: Springer handbook of marine biotechnology. Springer, pp 431–440.
  67. 67.
    Satheesh S, Ba-akdah MA, Al-Sofyani AA (2016) Natural antifouling compound production by microbes associated with marine macroorganisms: a review. Electron J Biotechnol 19:26–35. CrossRefGoogle Scholar
  68. 68.
    Makwana M, Grover CR, Kumar N (2018) Biocides resistance profiles of biofilm forming bacteria of dairy niche and their control. Int J Curr Microbiol App Sci 7:1194–1205. CrossRefGoogle Scholar
  69. 69.
    Heindl JE, Wang Y, Heckel BC, Mohari B, Feirer N, Fuqua C (2014) Mechanisms and regulation of surface interactions and biofilm formation in Agrobacterium. Front Plant Sci 5:176. CrossRefGoogle Scholar
  70. 70.
    e Silva S, Carvalho J, Aires C, Nitschke M (2017) Disruption of Staphylococcus aureus biofilms using rhamnolipid biosurfactants. J Dairy Sci 100:7864–7873. CrossRefGoogle Scholar
  71. 71.
    De Rienzo MAD, Banat IM, Dolman B, Winterburn J, Martin PJ (2015) Sophorolipid biosurfactants: possible uses as antibacterial and antibiofilm agent. N Biotechnol 32:720–726. CrossRefGoogle Scholar
  72. 72.
    Rendueles O, Ghigo J-M (2015) Mechanisms of competition in biofilm communities. Microbiol Spectr 3:1–18. CrossRefGoogle Scholar
  73. 73.
    Tannières M, Lang J, Barnier C, Shykoff JA, Faure D (2017) Quorum-quenching limits quorum-sensing exploitation by signal-negative invaders. Sci Rep 7:40126. CrossRefGoogle Scholar
  74. 74.
    Mu H, Tang J, Liu Q, Sun C, Wang T, Duan J (2016) Potent antibacterial nanoparticles against biofilm and intracellular bacteria. Sci Rep 6:18877. CrossRefGoogle Scholar
  75. 75.
    Ramasamy M, Lee J (2016) Recent nanotechnology approaches for prevention and treatment of biofilm-associated infections on medical devices. Biomed Res Int 2016:1851242. CrossRefGoogle Scholar

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© Association of Microbiologists of India 2018

Authors and Affiliations

  1. 1.Faculty of Life Sciences and BiotechnologySouth Asian UniversityNew DelhiIndia

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