Biofilm Microenvironments: Modeling Approach

  • Saheli Ghosh
  • Asifa QureshiEmail author
  • Hemant J. Purohit


Biofilms are resilient and complex microbial communities or populations encased in a self-producing extracellular matrix existing in nature, which account for their robustness against a wide variety of stresses. In nature, multispecies biofilms have been found to occur frequently, whereas monospecies biofilms have been rare and found only when developed. By understanding the sociobiology of biofilm bacteria and harnessing the knowledge based on known biochemical and physical parameters, the underlying complexity of biofilm microenvironment could be better predicted by state-of-the-art advanced modeling approaches. In the present review, in-depth advanced modeling approaches based on the action of substrates on developmental biofilm physiology have been discussed. Equations for forces and adherence, quorum sensing, fluid flow dynamics, the social arrangement of community members in their favorable places, stratification, and pattern formation inside the biofilm have been elaborated. Equations to predict biofilm dispersal stages have been also discussed. Different models which uncover microbial biofilm life cycle stages to predict their complexity and recommended future variables like “omics” for magnification have been reported. This chapter will help to provide additional platform related to the genetic complex networking of biofilm bacteria for conceptual underpinnings of biofilm microenvironment.


Biofilms Models Simulation Omics Quorum sensing Fluid flow 



Capillary electrophoresis-time of flight


Confocal laser scanning microscopy


Conductive-probe atomic force microscopy


Electrospray ionization mass spectrometry


Flux balance analysis


Fluorescent in situ hybridization


High-pH anion-exchange chromatography


Imaging mass spectrometry


Matrix-associated laser desorption ionization-time of flight


Mass spectrometry-desorption electrospray ionization


Pulsed amperometric detection


Polymerase chain reaction


Scanning transmission X-ray microscopy


Tipped enhanced Raman spectroscopy


X-ray microscopy



The authors are grateful to CSIR-Senior Research Fellowship for Ms. Saheli Ghosh (19-06/2011(i) EU-IV). Funds from DST, New Delhi (DST/TM/WTI/2K15/225(G)-A), and CSIR-NEERI for 12th plan network project (ESC0306 Activity No 3.4.2) on “Clean Water: sustainable options” are acknowledged. All the authors are thankful to Director of CSIR-National Environmental Engineering Research Institute (CSIR-NEERI) for constant support and inspiration and providing infrastructural facilities [CSIR-NEERI/KRC/2017/July/EBGD/14].


  1. Aparna MS, Yadav S (2008) Biofilms: microbes and disease. Braz J Infect Dis 12:526–530. CrossRefPubMedGoogle Scholar
  2. Arya R, Princy SA (2016) Exploration of modulated genetic circuits governing virulence determinants in Staphylococcus aureus. Indian J Microbiol 56:19–27. CrossRefPubMedGoogle Scholar
  3. Bazire A, Diab F, Jebbar M, Haras D (2007) Influence of high salinity on biofilm formation and benzoate assimilation by Pseudomonas aeruginosa. J Ind Microbiol Biotechnol 34:5–8. CrossRefPubMedGoogle Scholar
  4. Biggs MB, Papin JA (2013) Novel multiscale modeling tool applied to Pseudomonas aeruginosa biofilm formation. PLoS One 8:e78011. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cerca N, Gomes F, Pereira S, Teixeira P, Oliveira R (2012) Confocal laser scanning microscopy analysis of S. epidermidis biofilms exposed to farnesol, vancomycin and rifampicin. BMX Res Notes 5:244. CrossRefGoogle Scholar
  6. Cesar N, Reffuveille F, Kathryn EF, Hancock REW (2013) The effect of nitroxides on swarming motility and biofilms, multicellular behaviors in Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:4877–4881. CrossRefGoogle Scholar
  7. Chakraborty C, Chowdhury R, Bhattacharya P (2011) Experimental studies and mathematical modelling of an up flow biofilm reactor treating mustard oil-rich wastewater. Bioresour Technol 102:5596–5601. CrossRefPubMedGoogle Scholar
  8. Chang YM, Jeng WY, Ko TP, Yeh YJ, Chen CKM, Wang AHJ (2009) Structural study of TcaR and its complexes with multiple antibiotics from Staphylococcus epidermidis. PNAS 0913302107:1–6. CrossRefGoogle Scholar
  9. D’Acunto B, Esposito G, Frunzo L, Mattei MR, Pirozzi F (2013) Analysis and simulations of the initial phase in multispecies biofilm formation. Comm Appl Ind Math 4:e-448. CrossRefGoogle Scholar
  10. Das K, Rajawat MVS, Saxena AK, Prasanna R (2017) Development of Mesorhizobium ciceri-based biofilms and analyses of their antifungal and plant growth promoting activity in chickpea challenged by Fusarium wilt. Indian J Microbiol 57:48. CrossRefPubMedGoogle Scholar
  11. Davit Y, Byrne H, Osborne J, Pitt-Francis J, Gavaghan D, Quintard M (2013) Hydrodynamic dispersion within porous biofilms. Phys Rev E Stat Nonlinear Soft Math Phys 87:012718. CrossRefGoogle Scholar
  12. DeMello JMM, Brandao HL, De Souza AAU, Da Silva A, DeSouza SMAGU (2010) Biodegradation of BTEX compounds in a biofilm reactormodeling and simulation. J Pet Sci Eng 70:131–139. CrossRefGoogle Scholar
  13. Deygout C, Lesnec A, Campilloa F, Rapaport A (2013) Homogenized model linking microscopic and macroscopic dynamics of a biofilm: application to growth in a plug flow reactor. Ecol Model 250:15–24. CrossRefGoogle Scholar
  14. Dodds MG, Grobe KJ, Stewart PS (2000) Modeling biofilm antimicrobial resistance. Biotechnol Bioeng 68:456–465. CrossRefPubMedGoogle Scholar
  15. Ehret AE, Böl M (2013) Modeling mechanical characteristics of microbial biofilms by network theory. J R Soc Interface 10:20120676. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Fagerlind MG, Webb JS, Barraud N, McDougald D, Jansson A, Nilsson P, Harlen M, Kjelleberg S, Rice SA (2012) Dynamic modeling of cell death during biofilm development. J Theor Biol 295:23–36. CrossRefPubMedGoogle Scholar
  17. Frederick MR, Kuttler C, Hense BA, Eberl HJ (2011) A mathematical model of quorum sensing regulated EPS production in biofilm communities. Theory Biol Med Model 8:8. CrossRefGoogle Scholar
  18. Friedman A, Hu B, Xue C (2014) On a multiphase multicomponent model of biofilm growth. Arc Rat Mec Anal 211:257–300. CrossRefGoogle Scholar
  19. Ghosh S, Qureshi A, Purohit HJ (2017) Enhanced expression of catechol 1,2 dioxygenase gene in biofilm forming Pseudomonas mendocina EGD-AQ5 under increasing benzoate stress. Int Biodeterior Biodegrad 118:57–65. CrossRefGoogle Scholar
  20. Gokcen A, Vilcinskas A, Wiesner J (2013) Methods to identify enzymes that degrade the main extracellular polysaccharide component of Staphylococcus epidermidis biofilms. Virulence 4:260–270. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Golus J, Stankevic M, Sawicki R, Los R, Malm A, Ginalska G (2013) Quantitative analysis of biofilm formed on vascular prostheses by Staphylococcus epidermidis with different ica and aap genetic status. Int J Artif Organs 36:105–112. CrossRefPubMedGoogle Scholar
  22. Gui Z, Wang H, Ding T, Zhu W, Zhuang X, Chu W (2014) Azithromycin reduces the production of α-hemolysin and biofilm formation in Staphylococcus aureus. Indian J Microbiol 54:114–117. CrossRefPubMedGoogle Scholar
  23. Halan B, Buehler K, Schmid A (2012) Biofilms as living catalysts in continuous chemical synthesis. Trends Biotechnol 30:453–465. CrossRefPubMedGoogle Scholar
  24. Houry A, Gohar M, Deschamps J, Tischenko E, Aymerich S, Gruss A, Briandet R (2012) Bacterial swimmers that infiltrate and take over the biofilm matrix. PNAS 109:13088–13093. CrossRefPubMedGoogle Scholar
  25. Judith HM, Daniel EK, O’Toole GA (2011) Growing and analyzing static biofilms. Curr Protoc Microbiol. Unit.1B.1. CrossRefGoogle Scholar
  26. Kalia VC (2014) Microbes, antimicrobials and resistence: the battle goes on. Indian J Microbiol 54:1–2. CrossRefPubMedGoogle Scholar
  27. Kalia VC, Purohit HJ (2011) Quenching the quorum sensing system: potential antibacterial drug targets. Crit Rev Microbiol 37:121–140. CrossRefPubMedGoogle Scholar
  28. Kalia VC, Prakash J, Koul S, Ray S (2017) Simple and rapid method for detecting biofilm forming bacteria. Indian J Microbiol 57:109–111. CrossRefPubMedGoogle Scholar
  29. Kapley A, Purohit HJ (2009) Genomic tools in bioremediation. Indian J Microbiol 49:108–113. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kaur J, Niharika N, Lata P, Rup L (2014) Biofilms: united we stand, divided we fall. Indian J Microbiol 54:246–247. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kim J, Kim HS, Han S, Lee JY, Oh JE, Chung S, Park HD (2013) Hydrodynamic effects on bacterial biofilm development in a microfluidicMicrobial biofilms: current research and applications environment. Lab Chip 13:1846–1849. CrossRefPubMedGoogle Scholar
  32. 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. CrossRefPubMedGoogle Scholar
  33. 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. CrossRefPubMedGoogle Scholar
  34. Lear G, Lewis GD (2012) Microbial biofilms: current research and applications. Caister Academic press, Wymondham. ISBN: 978-1-904455-96-7Google Scholar
  35. Lee J, Wu J, Deng Y, Wang J, Wang C, Wang J, Chang C, Dong Y, Paul W, Zhang LH (2013) A cell-cell communication signal integrates quorum sensing and stress response. Nat Chem Biol 9:339–343. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Liao N, Li H (2013) Conceivable bioremediation techniques based on quorum sensing. Appl Mech Mater 295:39–44. CrossRefGoogle Scholar
  37. Liao Q, Wang YJ, Wang YZ, Chen R, Zhu X, Pu Y, Lee D (2012) Two-dimensional mathematical modeling of photosynthetic bacterial biofilm growth and formation. Int J Hydrog Energy 37:15607–15615. CrossRefGoogle Scholar
  38. Lin YH, Lin WF, Zhang KN, Lin PY, Lee MC (2013) Adsorption with biodegradation for decolorization of reactive black 5 by Funalia trogii 200800 on a fly ash chitosan medium in a fluidized bed bioreactor kinetic model and reactor performance. Biodegradation 24:137–152. CrossRefPubMedGoogle Scholar
  39. Llie O, van Loosedrechet MCM, Picioreanu C (2012) Mathematical modeling of tooth demineralization and pH profiles in dental plaques. J Theor Biol 309:159–175. CrossRefGoogle Scholar
  40. Martin KJ, Piciorean C, Nerenberg R (2013) Multidimensional modeling of biofilm development and fluid dynamics in a hydrogen-based, membrane biofilm reactor (MBfR). Water Res 47:4739–4751. CrossRefPubMedGoogle Scholar
  41. Mina P, di Bernardo M, Savery NJ, Atanasova KT (2013) Modelling emergence of oscillations in communicating bacteria: a structured approach from one to many cells. J R Soc Interface 10:20120612. CrossRefPubMedPubMedCentralGoogle Scholar
  42. Molloy S (2013) Biofilm microanatomy. Nat Rev Microbiol 11:300–301. CrossRefPubMedGoogle Scholar
  43. Momeni B, Brileya KA, Fields MW, Shou W (2013) Strong inter-population cooperation leads to partner intermixing in microbial communities. Elife 2:e00230. CrossRefPubMedPubMedCentralGoogle Scholar
  44. Moreira JMR, Teodósio JS, Silva FC, Simões M, Melo LF, Mergulhão FJ (2013) Influence of flow rate variation on the development of Escherichia coli biofilms. Bioprobiosys Eng 36:1787–1796. CrossRefGoogle Scholar
  45. Moustaid F, Eladdadi A, Uys L (2013) Modeling bacterial attachment to surfaces as an early stage of biofilm development. Math Biosci Eng 10:821–842. CrossRefPubMedGoogle Scholar
  46. Muthukaruppan S, Eswari A, Rajendran L (2013) Mathematical modeling of a biofilm: the Adomian decomposition method. Nat Sci 5:456–462. CrossRefGoogle Scholar
  47. Nadell CD, Bucci V, Drescher K, Levin SA, Bassler BL, Xavier JB (2013) Cutting through the complexity of cell collectives. Proc R Soc B 280:2012–2770. CrossRefGoogle Scholar
  48. Ni BJ, Yu HQ (2010) Mathematical modeling of aerobic granular sludge: a review. Biotechnol Adv 28:895–909. CrossRefPubMedGoogle Scholar
  49. O’Toole GA (2011) Microtiter dish biofilm formation assay. J Vis Exp 30:2437. CrossRefGoogle Scholar
  50. Pal S, Qureshi A, Purohit HJ (2016) Antibiofilm activity of biomolecules: gene expression study of bacterial isolates from brackish and fresh water biofouled membranes. Biologia 71:239–246. CrossRefGoogle Scholar
  51. Pantanella F, Valenti P, Natalizi T, Passeri D, Berlutti F (2013) Analytical techniques to study microbial biofilm on abiotic surfaces: pros and cons of the main techniques currently in use. Ann Ig 25:31–42. CrossRefPubMedGoogle Scholar
  52. Perez J, Picioreanu C, van Loosdrecht M (2005) Modeling biofilm and floc diffusion process based on analytical solution of reaction-diffusion equations. Water Res 39:1311–1323. CrossRefPubMedGoogle Scholar
  53. Picioreanu C, Kreft JU, Vanloosedrecht MCM (2004) Particle based multidimensional multispecies biofilm model. Appl Environ Microbiol 70:3024–3040. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Piubeli F, de Lourdes Moreno M, Kishi LT, Silva FH, Garcia MT, Mellado M (2015) Phylogenetic profiling and diversity of bacterial communities in the death valley, an extreme habitat in the Atacama Desert. Indian J Microbiol 55:392–399. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Purkait D, Ahuja A, Bhattacharjee U, Singha A, Rhetso K, Dey TK, Das S, Sanjukta RK, Puro K, Shakuntala I, Banerjee A, Sharma I, Bhatta RS, Mawlong M, Guha C, Pradhan NR, Ghatak S (2016) Molecular characterization and computational modelling of New Delhi metallo-β -lactamase-5 from an Escherichia coli isolate (KOEC3) of bovine origin. Indian J Microbiol 56:182–189. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Qi X, Nellas RB, Byrn MW, Russell MH, Bible AN, Alexandre G, Shen T (2013) Swimming motility plays a key role in the stochastic dynamics of cell clumping. Phys Biol 10:026005. CrossRefPubMedGoogle Scholar
  57. Qureshi A, Mohan M, Kanade GS, Kapley A, Purohit HJ (2009) In-situ bioremediation of organochlorine pesticide contaminated microcosm soil and evaluation by gene probe. Pest Manag Sci 65:798–804. CrossRefPubMedGoogle Scholar
  58. Qureshi A, Kapley A, Purohit HJ (2012) Degradation of 2,4,6-trinitrophenol (TNP) by Arthrobacter sp. HPC1223 isolated from effluent treatment plant. Indian J Microbiol 52:642–647. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Qureshi A, Pal S, Ghosh S, Kapley A, Purohit HJ (2015) Antibiofouling biomaterials. Int J Recent Adv Multidiscip Res (IJRAMR) 2:677–684Google Scholar
  60. Radu AI, Vrouwenvelder JS, van Loosedrecht MCM, Picioreanu C (2010) Modeling the effect of biofilm formation on reverse osmosis performance: flux, feed channel pressure drop and solute passage. J Membr Sci 365:1–15. CrossRefGoogle Scholar
  61. Roberts ME, Stewart PS (2004) Modeling antibiotic tolerance in biofilms by accounting for nutrient limitation. Antimicrob Agents Chemother 48:48–52. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Samso R, Garcia J (2013) BIO_PORE, a mathematical model to simulate biofilm growth and water quality improvement in porous media: application and calibration for constructed wetlands. Ecol Eng 54:116–127. CrossRefGoogle Scholar
  63. Shang Z, Wang H, Zhou S, Chu W (2014) Characterization of N-acyl-homoserine lactones (AHLs)-deficient clinical isolates of Pseudomonas aeruginosa. Indian J Microbiol 54:158–162. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Sharma A, Lal R (2017) Survey of (meta)genomic approaches for understanding microbial community dynamics. Indian J Microbiol 57:23–38. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Shen L, Lu Y, Liu Y (2012) Mathematical modeling of biofilm-covered granular activated carbon: a review. J Chem Technol Biotechnol 87:1513–1520. CrossRefGoogle Scholar
  66. Stewart PS, Costerton JW (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358:135–138. CrossRefPubMedGoogle Scholar
  67. VanderWal A, Tecon R, Kreft JU, Mooij WM, Leveau JHJ (2013) Explaining bacterial dispersion on leaf surfaces with an individual-based model (PHYLLOSIM). PLoS One 8:e75633. CrossRefGoogle Scholar
  68. Wang Q, Zhang T (2010) Review of mathematical models for biofilms. Sol St Comm 150:1009–1022. CrossRefGoogle Scholar
  69. Wang ZW, Hamilton-Brehm SD, Lochner A, Elkins JG, Morrell-Falvey JL (2012) Mathematical modeling of hydrolysate diffusion and utilization in cellulolytic biofilms of extreme thermophile Caldicellulosiruptor obsidiansis. Bioresour Technol 102:3155–3162. CrossRefGoogle Scholar
  70. Watrous JD, Phelan VV, Hsu CC, Moree WJ, Duggan BM, Alexandrov T, Dorrestein PC (2013) Microbial metabolic exchange in 3D. ISME J 7:770–780. CrossRefPubMedPubMedCentralGoogle Scholar
  71. Welch K, Cai Y, Stromme M (2012) A method for quantitative determination of biofilm viability. J Funct Biomater 3:418–431. CrossRefPubMedPubMedCentralGoogle Scholar
  72. Winter G, Krömer JO (2013) Fluxomics – connecting ‘omics analysis and phenotypes. Environ Microbiol 15:1901–1916. CrossRefPubMedGoogle Scholar
  73. Yong YC, Zhong JJ (2013) Regulation of aromatics biodegradation by rhl quorum sensing system through induction of catechol meta-cleavage pathway. Bioresour Technol 136:761–765. CrossRefPubMedGoogle Scholar
  74. Yoon S, Kim K, Kim JK (2013) Live-cell imaging of swarming bacteria in a fluidic biofilm formed on a soft agar gel substrate. J Vis 16:123–131. CrossRefGoogle Scholar
  75. Zarraonaindia I, Smith DP, Gilbert JA (2013) Beyond the genome: community-level analysis of the microbial world. Biol Philos 28:261–282. CrossRefPubMedGoogle Scholar
  76. Zhang T, Cogan N, Wang Q (2008) Phase field models for biofilms. I. Theory and one-dimensional simulations. SIAM J Appl Math 69:641–669. CrossRefGoogle Scholar
  77. Zhang W, Sileika T, Packman AI (2013) Effects of fluid flow conditions on interactionsbetween species in biofilms. FEMS Microbiol Ecol 84:344–354. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • Saheli Ghosh
    • 1
  • Asifa Qureshi
    • 1
    Email author
  • Hemant J. Purohit
    • 1
  1. 1.Environmental Biotechnology and Genomics DivisionCSIR – National Environmental Engineering and Research Institute (NEERI)NagpurIndia

Personalised recommendations