The renaissance of continuous culture in the post-genomics age

  • Alan T. BullEmail author


The development of continuous culture techniques 60 years ago and the subsequent formulation of theory and the diversification of experimental systems revolutionised microbiology and heralded a unique period of innovative research. Then, progressively, molecular biology and thence genomics and related high-information-density omics technologies took centre stage and microbial growth physiology in general faded from educational programmes and research funding priorities alike. However, there has been a gathering appreciation over the past decade that if the claims of systems biology are going to be realised, they will have to be based on rigorously controlled and reproducible microbial and cell growth platforms. This revival of continuous culture will be long lasting because its recognition as the growth system of choice is firmly established. The purpose of this review, therefore, is to remind microbiologists, particularly those new to continuous culture approaches, of the legacy of what I call the first age of continuous culture, and to explore a selection of researches that are using these techniques in this post-genomics age. The review looks at the impact of continuous culture across a comprehensive range of microbiological research and development. The ability to establish (quasi-) steady state conditions is a frequently stated advantage of continuous cultures thereby allowing environmental parameters to be manipulated without causing concomitant changes in the specific growth rate. However, the use of continuous cultures also enables the critical study of specified transition states and chemical, physical or biological perturbations. Such dynamic analyses enhance our understanding of microbial ecology and microbial pathology for example, and offer a wider scope for innovative drug discovery; they also can inform the optimization of batch and fed-batch operations that are characterized by sequential transitions states.


Continuous culture Theory and applications Chemostat Microbial behaviour Systems biology Microbial physiology Ecophysiology Pathology Steady state and transition state growth 



It is a pleasure to acknowledge the inspirational inputs of numerous students and post-docs in my group over so many years, and of the wider community of continuous culturalists the names of most of whom can be found in Table 2 and from whose friendship my thinking and research has greatly benefited. My thanks to those colleagues who sent me papers prior to publication. Michael Bushell read the review at draft stage and provided valuable comments. This review is dedicated to the next generation of scientists who will carry the torch for continuous culture.


  1. 1.
    Aboka FO, Heijnen JJ, van Winden WA (2009) Dynamic 13C-tracer study of storage carbohydrate pools in aerobic glucose-limited Saccharomyces cerevisiae confirms a rapid steady-state turnover and fast mobilization during a modest stepup in the glucose uptake rate. FEMS Yeast Res 9:191–201PubMedCrossRefGoogle Scholar
  2. 2.
    Agawin NSR, Rabouille S, Veldhuis MJW, Servatius L, Hol S, van Overzee MJ, Huisman J (2007) Competition and facilitation between unicellular nitrogen-fixing cyanobacteria and non-nitrogen-fixing phytoplankton species. Limnol Oceanogr 52:2233–2248Google Scholar
  3. 3.
    Alain K, Postec A, Grinsard E, Lesongeur F, Prieur D, Godfroy A (2010) Thermodesulfatator atlanticus sp. nov., a thermophilic, chemolithoautotrophic, sulfate-reducing bacterium isolated from a Mid-Atlantic Ridge hydrothermal vent. Int J Syst Evol Microbiol 60:33–38PubMedCrossRefGoogle Scholar
  4. 4.
    Ang CS, Vieth PD, Dashper SG, Reynolds EC (2008) Application of 16O/18O reverse proteolytic labeling to determine the effect of biofilm culture on the cell envelope proteome of Porphyyromonas gingivalis W50. Proteomics 8:1645–1660PubMedCrossRefGoogle Scholar
  5. 5.
    Arvas M, Pakula T, Lanthaler K, Saloheimo M, Valkonen M, Suortti T, Robson G, Pentilla M (2006) Common features and interesting differences in transcriptional responses to secretion stress in the fungi Trichoderma reesei and Saccharomyces cerevisiae. BMC Genomics 7:32PubMedCrossRefGoogle Scholar
  6. 6.
    Avignone-Rossa C, White J, Kuiper A, Postma PW, Bibb MJ, Texeira de Mattos MJ (2002) Carbon flux distribution in chemostat cultures of Streptomyces lividans. Metab Eng 4:138–150PubMedCrossRefGoogle Scholar
  7. 7.
    Baart GJE, Zomer B, de Haan A, van der Pol LA, Beuvery EC, Tramper J, Martens DE (2007) Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes. Genome Biol 8:r136PubMedCrossRefGoogle Scholar
  8. 8.
    Baart GJE, Willemsen M, Khatami E, de Haan A, Zomer B, Beuvery EC, Tramper J, Martens DE (2008) Modeling Neisseria meningitides B metabolism at different specific growth rates. Biotechnol Bioeng 101:1022–1035PubMedCrossRefGoogle Scholar
  9. 9.
    Babel W (2009) The auxiliary substrate concept: from simple considerations to heuristically valuable knowledge. Eng Life Sci 9:285–290CrossRefGoogle Scholar
  10. 10.
    Baines SD, Saxton K, Freeman J, Wilcox MH (2006) Tigecycline does not induce proliferation or cytotoxin production by epidemic Clostridium difficile strains in human gut model. J Antimicrob Chemother 58:1062–1065PubMedCrossRefGoogle Scholar
  11. 11.
    Balagadde FK, You LK, Hansen CL, Arnold FH, Quake SR (2005) Long-term monitoring of bacteria undergoing programmed population control in a microchemostat. Science 309:137–140PubMedCrossRefGoogle Scholar
  12. 12.
    Bastidas-Oyanedel JR, Aceves-Lara CA, Ruiz-Filippi G, Steyer JP (2008) Thermodynamic analysis of energy transfer in acidogenic cultures. Eng Life Sci 8:487–498CrossRefGoogle Scholar
  13. 13.
    Beste DJV, Peters J, Hooper C, Avignone–Rossa C, Bushell ME, McFadden JJ (2005) Compiling a molecular inventory for Mycobacterium bovis BCG at two growth rates: evidence for growth rate-mediated regulation of ribosome biosynthesis and lipid metabolism. J Bacteriol 187:1677–1684PubMedCrossRefGoogle Scholar
  14. 14.
    Beste DJV, Laing E, Bonde C, Avignone-Rossa C, Bushell ME, McFaddern JJ (2007) Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of Mycobacteria to survival inside the macrophage. J Bacteriol 189:3969–3976PubMedCrossRefGoogle Scholar
  15. 15.
    Beste DJV, Hooper T, Stewart G, Bonde B, Avignone-Rossa C, Bushell M, Wheeler P, Klamt S, Kierzek AM, McFadden JJ (2007) GSMN-TB: a web-based genome scale network model of Mycobacterium tuberculosis metabolism. Genome Biol 8:r89PubMedCrossRefGoogle Scholar
  16. 16.
    Beste DJV, Espasa M, Bonde B, Kierzek AM, Stewart GR, McFadden JJ (2009) The genetic requirements for fast and slow growth in mycobacteria. PLoS One 4:e5349PubMedCrossRefGoogle Scholar
  17. 17.
    Bijmans MFM, Dopson M, Peeters TWT, Lens PNL, Bujisman CJN (2009) Sulfate reduction at pH 5 in a high-rate membrane bioreactor: reactor performance and microbial community analyses. J Microbiol Biotechnol 19:698–708PubMedGoogle Scholar
  18. 18.
    Boer VM, Crutchfield CA, Bradley PH, Botstein D, Rabinowitz JD (2010) Growth-limiting intracellular metabolites in yeast growing under diverse nutrient limitations. Mol Biol Cell 21:198–211PubMedCrossRefGoogle Scholar
  19. 19.
    Boender LGM, de Huslster EAF, van Maris AJA, Daran-Lapujade PAS, Pronk JT (2009) Quantitative physiology of Saccharomyces cerevisiae at near-zero specific growth rates. Appl Environ Microbiol 75:5607–5614PubMedCrossRefGoogle Scholar
  20. 20.
    Bragg JG, Wagner A (2007) Protein carbon content evolves in response to carbon availability and may influence the fate of duplicated genes. Proc R Soc B 274:1063–1070PubMedCrossRefGoogle Scholar
  21. 21.
    Bragg JG, Wagner A (2009) Protein material costs: single atoms can make an evolutionary difference. Trends Genet 25:5–8PubMedCrossRefGoogle Scholar
  22. 22.
    Brauer MJ, Huttenhower C, Airoldi EM, Rosenstein R, Matese JC, Gresham D, Boer VM, Troyanskaya OG, Botstein D (2008) Coordination of growth rate, cell cycle, stress response, and metabolic activity in yeast. Mol Biol Cell 19:352–367PubMedCrossRefGoogle Scholar
  23. 23.
    Brenner S (2010) Sequences and consequences. Phil Trans R Soc B 365:207–212PubMedCrossRefGoogle Scholar
  24. 24.
    Breslauer DN, Lee PJ, Lee LP (2006) Microfluidics-based systems biology. Mol Bio Syst 2:97–112CrossRefGoogle Scholar
  25. 25.
    Brown SW, Oliver SG (1982) Isolation of ethanol-tolerant mutants of yeast by continuous selection. Eur J Appl Microbiol Biotechnol 16:119–122CrossRefGoogle Scholar
  26. 26.
    Bull AT (1974) Microbial growth. In: Bull AT, Lagnado JR, Thomas JO, Tipton KF (eds) Companion to biochemistry–selected topics for further study. Longman, London, pp 415–442Google Scholar
  27. 27.
    Bull AT (1983) Continuous culture for production. In: Hollaender A, Laskin AI, Rogers P (eds) Basic biology of new developments in biotechnology. Plenum, New York, pp 405–437Google Scholar
  28. 28.
    Bull AT (1985) Mixed culture and mixed substrate systems. In: Bull AT, Dalton H (eds) Comprehensive biotechnology, vol 1. The principles of biotechnology: scientific fundamentals. Pergamon, Oxford, pp 281–299Google Scholar
  29. 29.
    Bull AT, Brown CM (1979) Continuous culture applications to microbial biochemistry. In: Quayle JR (ed) International review of biochemistry, vol 21: microbial biochemistry. University Park Press, Baltimore, pp 177–226Google Scholar
  30. 30.
    Bull AT, Trinci APJ (1977) The physiology and metabolic control of fungal growth. Adv Microbial Physiol 15:1–84CrossRefGoogle Scholar
  31. 31.
    Bull DN, Young MD (1982) Enhanced product formation in continuous fermentations with microbial cell recycle. Biotechnol Bioeng 23:373–389CrossRefGoogle Scholar
  32. 32.
    Bushell ME, Kirk S, Zhao HJ, Avignone-Rossa C (2006) Manipulation of the physiology of clavulanic acid biosynthesis with the aid of metabolic flux analysis. Enzyme Microb Technol 39:149–157CrossRefGoogle Scholar
  33. 33.
    Bushell ME, Sequeira SIP, Khannapho C, Zhao HJ, Chater KF, Butler MJ, Kierzek AJM, Avignone-Rossa C (2006) The use of genome scale metabolic flux variability analysis for process feed formulation based on an investigation of the effects of the zwf mutation on antibiotic production in Streptomyces coelicolor. Enzyme Microb Technol 39:1347–1353CrossRefGoogle Scholar
  34. 34.
    Canelas AB, ten Pierick A, Ras C, Seifar RM, van Dam JC, van Gulik WM, Heijnen JJ (2009) Quantitative evaluation of intracellular metabolite extraction techniques for yeast metabolomics. Anal Chem 81:7379–7389PubMedCrossRefGoogle Scholar
  35. 35.
    Carlile MJ, Skehel JJ (eds) (1974) Evolution in the microbial world, pp i–x, 1–430, symposium 24 Soc Gen Microbiol, Cambridge University Press, CambridgeGoogle Scholar
  36. 36.
    Chong L, Ray LB (2002) Whole-istic biology. Science 295:1661CrossRefGoogle Scholar
  37. 37.
    Chrzanowski TH, Grover JP (2008) Element content of Pseudomonas fluorescens varies with growth rate and temperature: a replicated chemostat study addressing ecological stoichiometry. Limnol Oceanogr 53:1242–1251Google Scholar
  38. 38.
    Cipollina C, van den Brink J, Daran-Lapujade P, Pronk JT, Porro D, de Winde JH (2008) Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis. Microbiology 154:1686–1699PubMedCrossRefGoogle Scholar
  39. 39.
    Clarke PH, Lilly MD (1969) The regulation of enzyme synthesis during growth. In: Meadows PM, Pirt SJ (eds) Microbial growth, symposium 19 Soc Gen Microbiol. Cambridge University Press, Cambridge, pp 113–159Google Scholar
  40. 40.
    Codeco CT, Grover JP (2001) Competition along a spatial gradient of resource supply: a microbial experimental model. Am Nat 157:300–315PubMedCrossRefGoogle Scholar
  41. 41.
    Cooper DC, Copeland BJ (1973) Responses of continuous-series estuarine microecosytems to point source input variations. Ecol Monogr 43:213–236CrossRefGoogle Scholar
  42. 42.
    Cornejo OE, Rozen DE, May RM, Levin BR (2008) Oscillations in continuous cultures populations of Streptococcus pneumoniae: population dynamics and evolution of clonal suicide. Proc R Soc B 276:999–1008CrossRefGoogle Scholar
  43. 43.
    Crane KW, Grover JP (2010) Coexistence of mixotrophs, autotrophs, and heterotrophs in planktonic microbial communities. J Theor Biol 262:517–527PubMedCrossRefGoogle Scholar
  44. 44.
    Daran-Lapujade P, Jansen MLA, Daran JM, van Gulik W, de Winde JH, Pronk JT (2004) Role transcriptional regulation in controlling fluxes in central carbon metabolism of Saccharomyces cerevisiae–a chemostat study. J Biol Chem 279:9125–9138PubMedCrossRefGoogle Scholar
  45. 45.
    Daran-Lapujade P, Daran JM, van Maris AJA, de Winde JH, Pronk JT (2009) Chemostat-based micro-array analysis in baker’s yeast. Adv Microbial Physiol 54:257–311CrossRefGoogle Scholar
  46. 46.
    Dashper SG, Ang CS, Veith PD, Mitchell HL, Lo AWH, Seers CA, Walsh KA, Slakeski N, Chen D, Lissel JP, Butler CA, O’Brien-Simpson NM, Barr IG, Reynolds EC (2009) Response of Porphyromonas gingivalis to heme limitation in continuous culture. J Bacteriol 191:1044–1055PubMedCrossRefGoogle Scholar
  47. 47.
    Dean ACR, Ellwood DC, Melling J, Robinson A (1976) The action of antibacterial agents on bacteria grown in continuous culture. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous culture 6: applications and new fields. Ellis Horwood, Chichester, pp 251–261Google Scholar
  48. 48.
    de Crécy E, Metzgar D, Allen C, Pénicaud M, Lyons B, Hansen CJ, Crécy-Lagard V (2007) Development of a novel continuous culture devise for experimental evolution of bacterial populations. Appl Microbiol Biotechnol 77:489–496PubMedCrossRefGoogle Scholar
  49. 49.
    de Crécy E, Jaronski S, Lyons B, Lyons TJ, Keyhani NO (2009) Directed evolution of a filamentous fungus for thermotolerance. BMC Biotechnol 9:74PubMedCrossRefGoogle Scholar
  50. 50.
    Delneri D, Hoyle DC, Gkargkas K, Cross EJM, Rash B, Zeef L, Leong HS, Davey HM, Hayes A, Kell DB, Griffith GW, Oliver SG (2008) Identification and characterization of high-flux-control genes of yeast through competition analysis. Na Genet 40:113–117PubMedCrossRefGoogle Scholar
  51. 51.
    DellaGreca M, Zarelli A, Fergola P, Cerasuola M, Pollioi A, Pinto G (2010) Fatty acids released by Chlorella vulgaris and their role in interference with Pseudokirchneriella subcapita: experiments and modeling. J Chem Ecol 36:339–349PubMedCrossRefGoogle Scholar
  52. 52.
    De Nicola R, Hazelwood LA, De Hulster EAF, Walsh MC, Knijnenburg TA, Reinders MJT, Walker GM, Pronk JT, Daran JM, Daran-Lapujade (2007) Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc-limitation in chemostat cultures. Appl Environ Microbiol 73:7680–7692PubMedCrossRefGoogle Scholar
  53. 53.
    Diano A, Peeters J, Dynesen J, Nielsen J (2009) Physiology of Aspergillus niger in oxygen-limited continuous cultures: influence of aeration, carbon source concentration and dilution rate. Biotechnol Bioeng 103:956–965PubMedCrossRefGoogle Scholar
  54. 54.
    Droop MR (1968) Vitamin B12 and marine ecology. IV. The kinetics of uptake, growth and inhibition in Monochrysis butleri. J Protozool 48:689–733Google Scholar
  55. 55.
    Dye C, Williams BG (2010) The population dynamics and control of tuberculosis. Science 328:856861CrossRefGoogle Scholar
  56. 56.
    Elias DA, Tollaksen SL, Kennedy DW, Mottaz HM, Giometti CS, McLean JS, Hill EA, Punchuk GE, Lipton MS, Fredrickson JK, Gorby YA (2008) The influence of cultivation methods on Shewanella oneidensis physiology and proteome expression. Arch Microbiol 189:313–324PubMedCrossRefGoogle Scholar
  57. 57.
    Ellwood DC, Hunter JR (1976) The mouth as a chemostat. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous culture 6: applications and new fields. Ellis Horwood, Chichester, pp 270–282Google Scholar
  58. 58.
    Ferea TL, Botstein D, Brown PO, Rosenzweig RF (1999) Systematic changes in gene expression patterns following adaptive evolution in yeast. Proc Nat Acad Sci U S A 96:9721–9726CrossRefGoogle Scholar
  59. 59.
    Ferenci T (1999) Growth of bacterial cultures 50 years on: towards an uncertainty principle instead of constants in bacterial growth kinetics. Res Microbiol 150:431–438PubMedCrossRefGoogle Scholar
  60. 60.
    Ferenci T (2006) A cultural divide on the use of chemostats. Microbiology 152:1247–1248PubMedCrossRefGoogle Scholar
  61. 61.
    Ferenci T (2008) Bacterial physiology, regulation and mutational adaptation in a chemostat environment. Adv Microbial Phyisol 53:22–169Google Scholar
  62. 62.
    Fergola P, Cerasuolo M, Pollio A, Pinto G, DellaGreca M (2007) Allelopathy and competition between Chlorella vulgaris and Pseudokirchneriella subcapitata: experiments and mathematical model. Ecol Model 208:205–214CrossRefGoogle Scholar
  63. 63.
    Flynn KJ (2005) Castles built on sand: dysfunctionality in plankton models and the inadequacy of dialogue between biologists and modelers. J Plankton Res 27:1205–1210CrossRefGoogle Scholar
  64. 64.
    Flynn KJ (2008) Use, abuse, misconceptions and insights from quota models–the droop cell quota model 40 years on. Oceanogr Mar Biol An Rev 46:1–23CrossRefGoogle Scholar
  65. 65.
    Gefen O, Balaban NQ (2008) The Moore’s Law of microbiology–towards bacterial culture miniaturization with the micro-Petri chip. Trends Biotechnol 26:345–347PubMedCrossRefGoogle Scholar
  66. 66.
    Gerhardt P (1946) Brucella suis in aerated broth culture, III. Continuous culture studies. J Bacteriol 52:283–292PubMedGoogle Scholar
  67. 67.
    Gilbert A, Srienc F (2009) Optimized evolution in the cytostat: a Monte Carlo simulation. Biotechnol Bioeng 102:221–231PubMedCrossRefGoogle Scholar
  68. 68.
    Gilbert A, Sangurdekar DP, Scrienc F (2009) Rapid strain improvement through optimized evolution in the cytostat. Biotechnol Bioeng 103:500–512PubMedCrossRefGoogle Scholar
  69. 69.
    Golby P, Hatch KA, Bacon J, Cooney R, Riley P, Allnutt J, Hinds J, Nunez J, Marsh PD, Hewinson RG, Gordon SV (2007) Comparative transcriptomics reveals key gene expression differences between the human and bovine pathogens of the Mycobacterium tuberculosis complex. Microbiology 153:3323–3336PubMedCrossRefGoogle Scholar
  70. 70.
    Gresham D, Desai MM, Tucker CM, Jenq HT, Pai DA, Ward A, DeSevo CG, Botstein D, Dunham MJ (2008) The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLOS Genet 4:e1000303PubMedCrossRefGoogle Scholar
  71. 71.
    Groeneveld P, Stouthamer AH, Westerhoff HV (2009) Super life–how and why ‘cell selection’ leads to the fastest-growing eukaryote. FEBS J 276:254–270PubMedCrossRefGoogle Scholar
  72. 72.
    Groisman A, Lobo C, Campbell JK, Dufour YS, Stevens AM, Levchenko A (2005) A microfluidic chemostat for experiments with bacterial and yeast cells. Nat Methods 2:685–689PubMedCrossRefGoogle Scholar
  73. 73.
    Grover JP, Chrzanowski TH (2009) Dynamics and nutritional ecology of a nanoflagellate preying upon bacteria. Microb Ecol 58:231–243PubMedCrossRefGoogle Scholar
  74. 74.
    Guebel DV, Canovas M, Torres NV (2009) Analysis of the Escherichia coli response to glycerol pulse in continuous, high-cell density culture using a multivariate approach. Biotechnol Bioeng 102:910–922PubMedCrossRefGoogle Scholar
  75. 75.
    Hall BG (1985) Enzyme evolution. In: Bull AT, Dalton H (eds) Comprehensive biotechnology vol 1, the principles of biotechnology: scientific fundamentals. Pergamon, Oxford, pp 553–566Google Scholar
  76. 76.
    Hamer G (1984) Continuous culture kinetics and activated sludge processes. In: Dean ACR, Ellwood DC, Evans CGT (eds) Continuous culture 8: biotechnology, medicine and the environment. Ellis Horwood, Chichester, pp 169–184Google Scholar
  77. 77.
    Hamilton IR, Ellwood DC (1978) Effects of fluoride on carbohydrate metabolism by washed cells of Streptococcus mutans grown at various pH values in a chemostat. Infect Immun 19:434–442PubMedGoogle Scholar
  78. 78.
    Harder W, Dijkhuisen L (1976) Mixed substrate utilization. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous culture 6: applications and new fields. Ellis Horwood, Chichester, pp 297–314Google Scholar
  79. 79.
    Hardman DJ, Huxley M, Bull AT, Slater JH, Bates R (1997) Generation of environmentally enhanced products: clean technology for paper chemicals. J Chem Technol Biotechnol 70:60–66CrossRefGoogle Scholar
  80. 80.
    Harris DM, van der Krogt ZA, Klaasen P, Raamsdonk LM, Hage S, van den Berg MA, Bovenberg RAL, Pronk JT, Daran JM (2009) Exploring and dissecting genome-wide gene expression responses of Penicillium chrysogenum to phenylacetic acid and penicillin G. BMC Genomics 10:75PubMedCrossRefGoogle Scholar
  81. 81.
    Harrison DEF (1972) Physiological effects of dissolved oxygen tension and redox potential on growing populations of micro-organisms. In: Dean ACR, Pirt SJ, Tempest DW (eds) Continuous culture 5: environmental control of cell synthesis and function. Academic, London, pp 417–440Google Scholar
  82. 82.
    Harrison DEF, Topiwala HH, Hamer G (1972) Yield and productivity in single-cell protein production from methane and methanol. In: Terui G (ed) Proc IV Int Ferment Symp Fermentation Technology Today, pp 491–495Google Scholar
  83. 83.
    Harrison DEF, Wikinson TG, Wren SJ, Harwood JH (1976) Mixed bacterial cultures as a basis for continuous production of SCP from C1 compounds. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous culture 6: applications and new fields. Ellis Horwood, Chichester, pp 122–134Google Scholar
  84. 84.
    Hazelwood LA, Walsh MC, Luttik MAH, Daran-Lapujade P, Pronk JT, Daran JM (2009) Identity of the growth-limiting nutrient strongly affects storage carbohydrate accumulation in anaerobic chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microbiol 75:6876–6885PubMedCrossRefGoogle Scholar
  85. 85.
    Hendrickson EL, Haydock AK, Moore BC, Whitman WB, Leigh JA (2007) Functionally distinct genes regulated by hydrogen limitation and growth rate in methanogenic Archaea. Proc Nat Acad Sci U S A 104:8930–8934CrossRefGoogle Scholar
  86. 86.
    Hendrickson EL, Liu Y, Rosas-Sandoval G, Porat I, Soll D, Whitman WB, Leigh JA (2008) Global responses of Methanococcus maripaludis to specific nutrient limitations and growth rate. J Bacteriol 190:2198–2205PubMedCrossRefGoogle Scholar
  87. 87.
    Herbert D (1976) Stoichiometric aspects of microbial growth. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous culture 6: applications and new fields. Ellis Horwood, Chichester, pp 1–30Google Scholar
  88. 88.
    Herbert D, Elsworth R, Telling RC (1956) The continuous culture of bacteria: a theoretical and experimental study. J Gen Microbiol 14:601–622PubMedGoogle Scholar
  89. 89.
    Hospodka J (1966) Industrial application of continuous fermentation. In: Malék I, Fencl Z (eds) Theoretical and methodological basis of continuous culture of microorganisms. Czech Acad Sci, Prague, pp 493–645Google Scholar
  90. 90.
    Hough JS, Keevil CW, Maric C, Philliskirk G, Young TW (1976) Continuous culture brewing. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous culture 6: applications and new fields. Ellis Horwood, Chichester, pp 226–237Google Scholar
  91. 91.
    Huisman J, Matthijs HCP, Visser PM, Balke H, Sigon CAM, Passarge J, Weissing FJ, Mur LR (2002) Principles of the light-limited chemostat: theory and ecological applications. Antonie van Leeuwen 81:117–133CrossRefGoogle Scholar
  92. 92.
    Ingham CJ, Sprenkels A, Bomer J, Molenaar D, van den Berg A, Vlieg JETV, de Vos WM (2007) The micro-Petri dish, a million-well growth chip for the culture and high-throughput screening of microorganisms. Proc Nat Acad Sci U S A 104:18217–18222CrossRefGoogle Scholar
  93. 93.
    Ishii N et al (2007) Multiple high-throughput analyses monitor the response of E. coli to perturbations. Science 316: 593–597Google Scholar
  94. 94.
    Ives PR, Bushell ME (1997) Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus. Microbiol 143:3573–3579CrossRefGoogle Scholar
  95. 95.
    Jansen MLA, Diderich JA, Mashego M, Hassane A, de Winde JH, Daran-Lapujade P, Pronk JT (2005) Prolonged selection in aerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae causes a partial loss of glycolytic capacity. Microbiology 151:1657–1669PubMedCrossRefGoogle Scholar
  96. 96.
    Johri AK, Margarit I, Broenstrup M, Buttoni C, Hua L, Gygi SP, Telford JL, Grandi G, Paoletii LC (2007) Transcriptional and proteomic profiles of group B Streptococcus type V reveal potential adherence proteins associated with highlevel invasion. Infect Immun 75:1473–1483PubMedCrossRefGoogle Scholar
  97. 97.
    Jones LE, Ellner SP (2008) Effects of rapid prey evolution on predator-prey cycles. J Math Biol 55:541–573CrossRefGoogle Scholar
  98. 98.
    Kacmar J, Gilbert A, Cockrell J, Srienc (2006) The cytostat: a new way to study cell physiology in a precisely defined environment. J Biotechnol 125:163–172CrossRefGoogle Scholar
  99. 99.
    Khannapho C, Zhao H, Bonde BK, Kierzek AM, Avignone-Rossa CA, Bushell ME (2008) Selection of objective function in genome scale flux balance analysis for process feed development in antibiotic production. Metab Eng 10:227–233PubMedCrossRefGoogle Scholar
  100. 100.
    King T, Seeto S, Ferenci T (2006) Genotype-by-environment interactions influencing the emergence of rpoS mutations in Escherichia coli populations. Genetics 172:2071–2079PubMedCrossRefGoogle Scholar
  101. 101.
    Kirk S, Avignone-Rossa CA, Bushell ME (2000) Growth limiting substrate affects antibiotic production and associated metabolic fluxes in Streptomyces clavuligerus. Biotechnol Lett 22:1803–1809CrossRefGoogle Scholar
  102. 102.
    Kisand V, Rocker D, Simon M (2008) Significant decomposition of riverine humic-rich DOC by marine but not estuarine bacteria assessed in sequential chemostat experiments. Aquatic Microbial Ecol 53:151–160CrossRefGoogle Scholar
  103. 103.
    Kleijn RJ, Liu F, van Winden WA, van Gulik WA, Ras C, Heijnen JJ (2007) Cytosolic NADPH metabolism in penicillin-G producing and non-producing chemostat cultures of Penicillium chrysogenum. Metab Eng 9:12–123CrossRefGoogle Scholar
  104. 104.
    Knijnenburg TA, de Winde JH, Daran JM, Daran-Lapujade, Pronk JT, Reinders MJT, Wessels LFA (2007) Exploiting combinatorial cultivation conditions to infer regulation. BMC Genomics 8:25PubMedCrossRefGoogle Scholar
  105. 105.
    Koetsier MJ and 10 other authors (2010) The Penicillium chrysogenum aclA gene encodes a broad-substrate-specificity acyl-coenzyme A ligase involved in activation of adipic acid, a side-chain precursor for cephem antibiotics. Fungal Genet Biol 47: 33-42Google Scholar
  106. 106.
    Kolkman A, Daran-Lapujade P, Fullaondo A, Oisthoorn MMA, Pronk JT, Slijper M, Heck AJR (2006) Proteome analysis of yeast response to various nutrient limitations. Mol Syst Biol 2:026CrossRefGoogle Scholar
  107. 107.
    Kubitschek HE (1970) Introduction to research with continuous cultures. Prentice-Hall, Englewood Cliffs, pp iix, 1–195Google Scholar
  108. 108.
    Kuenen JG, Gottschahl JC (1982) Competition among chemolithotrophs and methylotrophs and their interactions with heterotrophic bacteria. In: Bull AT, Slater JH (eds) Microbial interactions and communities. Academic, London, pp 153–187Google Scholar
  109. 109.
    Lambert PA (1984) The role of the bacterial envelop in antibiotic resistance. In: Dean ACR, Ellwood DC, Evans CGT (eds) Continuous culture 8: biotechnology, medicine and the environment. Ellis Horwood, Chichester, pp 38–54Google Scholar
  110. 110.
    Lennon JT, Martiny JBH (2008) Rapid evolution buffers ecosystem impacts of viruses in a microbial food web. Ecol Lett 11:1178–1188PubMedGoogle Scholar
  111. 111.
    Li BZ, Cheng JS, Qiao B, Yuan YJ (2010) Genome-wide transcriptional analysis of Saccharomyces cereviseae during industrial bioethanol fermentation. J Ind Microbiol Biotechnol 37:43–55PubMedCrossRefGoogle Scholar
  112. 112.
    Lin B, Westerhoff, Roling WFM (2009) How Geobacteriaceae may dominate subsurface biodegradation: physiology of Geobacter metallireducens in slow growth habitat-simulating retentostats. Environ Microbiol 11:2425–2433PubMedCrossRefGoogle Scholar
  113. 113.
    Linton JD, Drozd JW (1982) Microbial interactions and communities in biotechnology. In: Bull AT, Slater JH (eds) Microbial interactions and communities. Academic, London, pp 357–406Google Scholar
  114. 114.
    Lo AW, Seers CA, Boyce JD, Dashper SG, Slakeski N, Lissel JP, Reynolds EC (2009) Comparative transcriptomic analysis of Porphyromonas gingivalis biofilm and planktonic cells. BMC Microbiol 9:18PubMedCrossRefGoogle Scholar
  115. 115.
    Lovitt RW, Wimpenny JWT (1981) The gradostat: a bidirectional compound chemostat, and its application in microbiological research. J Gen Microbiol 127:261–268PubMedGoogle Scholar
  116. 116.
    Luders S, Fallet C, Franco-Lara E (2009) Proteome analysis of the Escherichia coli heat shock response under steady-state conditions. Proteome Sci 7:36PubMedCrossRefGoogle Scholar
  117. 117.
    Luscombe BM, Gray TRG (1974) Characteristics of Arthrobacter grown in continuous culture. J Gen Microbiol 82:213–222Google Scholar
  118. 118.
    Macfarlane GT, Macfarlane S, Gibson G (1998) Validation of a three-stage compound continuous culture system for investigating the effect of retention time on the ecology and metabolism of bacteria in the human gut. Microbial Ecol 35:180–187CrossRefGoogle Scholar
  119. 119.
    Macfarlane GT, Macfarlane LE (2009) Acquisition, evolution and maintenance of the normal gut microbiota. Digestive Dis 27:90–98CrossRefGoogle Scholar
  120. 120.
    Maharjan R, Seeto S, Notley-McRobb L, Ferenci T (2006) Clonal adaptive radiation in a constant environment. Science 313:514–517PubMedCrossRefGoogle Scholar
  121. 121.
    Major NC, Bull AT (1989) The physiology of lactate production by Lactobacillus delbreuckii in a chemostat with cell recycle. Biotechnol Bioeng 34:592–599PubMedCrossRefGoogle Scholar
  122. 122.
    Majors PD, McLean JS, Scholten JCM (2008) NMR bioreactor development for live in situ microbial functional analysis. J Magn Reson 192:159–166PubMedCrossRefGoogle Scholar
  123. 123.
    Málek I (1976) Physiological state of continuously grown microbial cultures. In: Dean ACR, Ellwood DC, Evans CGT, Melling J (eds) Continuous Culture 6: Applications and New Fields. Ellis Horwood, Chichester, pp 31–39Google Scholar
  124. 124.
    Málek I, Fencl Z (eds) (1966) Theoretical and methodological basis of continuous culture of microorganisms. Czech Acad Sci, Prague, pp 1–655Google Scholar
  125. 125.
    Massie TM, Blasius B, Weithoff G, Gaedke U, Fussmann GF (2010) Cycles, phase synchronization, and entrainment in single-species phytoplankton populations. Proc Nat Acad Sci U S A 107:4236–4241CrossRefGoogle Scholar
  126. 126.
    McFadden J (2010) Systems biology and the TB bacillus. Microbiology Today 17:16–19Google Scholar
  127. 127.
    McIntyre JJ, Bunch AW, Bull AT (1999) Vancomycin production is enhanced in chemostat culture with biomass-recycle. Biotechnol Bioeng 62:576–582PubMedCrossRefGoogle Scholar
  128. 128.
    M’Kendrick AG, Pai MK (1911) The rate of multiplication of microorganisms, a mathematical study. Proc R Soc Edinb 31:649–655Google Scholar
  129. 129.
    Middelboe M, Holmfeldt K, Riemann L, Nybroe O, Haaber J (2009) Ba24 bacteriophages drive strain diversification in a marine Flavobacterium: implications for phage resistance. Environ Microbiol 11:1971–1982PubMedCrossRefGoogle Scholar
  130. 130.
    Minnikin DE, Abdolrahimzadeh H, Baddiley J (1972) Variation of polar lipid composition of Bacillus subtilis (Marburg) with different growth conditions. FEBS Lett 27:16–18PubMedCrossRefGoogle Scholar
  131. 131.
    Mitchell HL, Dashper SG, Catmull DV, Paolini RA, Cleal SM, Slakeski N, Tan KH, Reynolds EC (2010) Treponema denticola biofilm-induced expression of a bacteriophage, toxin-antitoxin systems and transposases. Microbiology 156:774–788PubMedCrossRefGoogle Scholar
  132. 132.
    Monod J (1949) The growth of bacterial cultures. Ann Rev Microbiol 3:371–394CrossRefGoogle Scholar
  133. 133.
    Monod J (1950) La technique de culture continuée. Theorie et application. Ann Inst Pasteur (Paris) 79:390–410Google Scholar
  134. 134.
    Muñoz-Aguayo J, Lang JK, LaPara TM, González G, Singer RS (2007) Evaluating the effects of chlortetracycline on the proliferation of antibiotic- resistant bacteria in a simulated river water ecosystem. Appl Environ Microbiol 73:5421–5425PubMedCrossRefGoogle Scholar
  135. 135.
    Nakhu R, Valgepea K, Lahtvee PJ, Erm S, Abner K, Adamberg K, Vilu R (2010) Specific growth rate dependent transcriptome profiling of Escherichia coli K12 MG1655 in accelerostat cultures. J Biotechnol 145:60–65CrossRefGoogle Scholar
  136. 136.
    Nanchen A, Schicker A, Revelles O, Sauer U (2008) Cyclic AMP-dependent catabolite repression is the dominant control mechanism of metabolic fluxes under glucose limitation in Escherichia coli. J Bacteriol 190:2323–2330PubMedCrossRefGoogle Scholar
  137. 137.
    Neijssel OM, Tempest DW (1976) Role of energy-spilling reactions in growth of Klebsiella aerogenes NCTC-418 in aerobic chemostat culture. Arch Microbiol 110:305–311PubMedCrossRefGoogle Scholar
  138. 138.
    Nicholls HA, Osborn DW, Buchan L, Melmed LN, Pitman AR (1984) Biological removal of phosphorus and nitrogen from waste water. In: Dean ACR, Ellwood DC, Evans CGT (eds) Continuous culture 8: biotechnology, medicine and the environment. Ellis Horwood, Chichester, pp 185–204Google Scholar
  139. 139.
    Nishikawa T, Guilbahce N, Motter AE (2008) Spontaneous reaction silencing in metabolic optimization. PLoS Comput Biol 4:e1000236PubMedCrossRefGoogle Scholar
  140. 140.
    Novick A, Szilard L (1950) Description of the chemostat. Science 112:715–716PubMedCrossRefGoogle Scholar
  141. 141.
    Novick A, Szilard L (1950) Experiments with the chemostat on spontaneous mutations of bacteria. Proc Nat Acad Sci U S A 36:708–719CrossRefGoogle Scholar
  142. 142.
    Parkes RJ (1982) Methods for enriching, isolating, and analysing microbial communities in laboratory systems. In: Bull AT, Slater JH (eds) Microbial interactions and communities. Academic, London, pp 45–102Google Scholar
  143. 143.
    Parkes RJ, Wellsbury P (2004) Deep biospheres. In: Bull AT (ed) Microbial diversity and bioprospecting. ASM, Washington, DC, pp 120–129Google Scholar
  144. 144.
    Partridge JD, Scott C, Tang Y, Poole RK, Green J (2006) Escherichia coli transcriptome dynamics during the transition from anaerobic to aerobic conditions. J Biol Chem 281:27806–27815PubMedCrossRefGoogle Scholar
  145. 145.
    Pickell LD, Wells ML, Trick CG, Cochlan WP (2009) A sea-going continuous culture system for investigating phytoplankton community response to macro- and micro-nutrient manipulations. Limnol Oceanogr Methods 7:21–32Google Scholar
  146. 146.
    Pir P, Kirdar B, Hayes A, Onsan ZI, Ulgen KO, Oliver SG (2008) Exometabolic and transcriptional response in relation to phenotype and gene copy number in respiration-related deletion mutants of S. cerevisiae. Yeast 25:661–672PubMedCrossRefGoogle Scholar
  147. 147.
    Pirt SJ (1965) The maintenance energy of bacteria in growing cultures. Proc R Soc B 163:224–231CrossRefGoogle Scholar
  148. 148.
    Pirt SJ (1975) Principles of microbe and cell culture. Blackwell, Oxford, pp i–x, 1–274Google Scholar
  149. 149.
    Pirt SJ, Kurowski WM (1970) Extension of theory of chemostat with feedback of organisms - its experimental realization with a yeast culture. J Gen Microbiol 63:357–366PubMedGoogle Scholar
  150. 150.
    Postec A, Lesongeur F, Oignet P, Ollivier B, Querellou J, Godfroy A (2007) Continuous enrichment cultures: insights into prokaryotic diversity and metabolic interactions in deep-sea vent chimneys. Extremophiles 11:747–757PubMedCrossRefGoogle Scholar
  151. 151.
    Primrose SB, Derbyshire P, Jones IM, Robinson A, Ellwood DC (1984) The application of continuous culture to the study of plasmid stability. In: Dean ACR, Ellwood DC, Evans CGT (eds) Continuous culture 8: biotechnology, medicine and the environment. Ellis Horwood, Chichester, pp 213–238Google Scholar
  152. 152.
    Pullan ST, Monk CE, Lee L, Poole RK (2008) Microbial responses to nitric oxide and nitrosative stress: growth, “omic”, and physiological methods. Methods Enzymol 437:499–519PubMedCrossRefGoogle Scholar
  153. 153.
    Rautio JJ, Smit BA, Wiebe M, Pentilla M, Saloheimo M (2006) Transcriptional monitoring of steady state and effects of anaerobic phases in chemostat cultures of the fungus Trichoderma reesei. BMC Genomics 7:247PubMedCrossRefGoogle Scholar
  154. 154.
    Revilla T, Weissing FJ (2008) Nonequilibrium coexistence in a competition model with nutrient storage. Ecology 89:865–877PubMedCrossRefGoogle Scholar
  155. 155.
    Robinson A, Gorringe AR, Keevil CW (1984) Expression of virulence determinants in Bordetella pertusis and Neisseria gonorrhoeae. In: Dean ACR, Ellwood DC, Evans CGT (eds) Continuous culture 8: biotechnology, medicine and the environment. Ellis Horwood, Chichester, pp 22–37Google Scholar
  156. 156.
    Rokem JS, Laantz AE, Nielsen J (2007) Systems biology of antibiotic production by microorganisms. Nat Prod Rep 24:1262–1287PubMedCrossRefGoogle Scholar
  157. 157.
    Rowley BI, Bull AT (1973) Chemostat for the cultivation of moulds. Lab Prac, April: 286–289Google Scholar
  158. 158.
    Russell JB (2007) The energy spilling reactions of bacteria and other organisms. J Mol Microbiol Biotechnol 13:1–11PubMedCrossRefGoogle Scholar
  159. 159.
    Russell DG, Barry CE, Flynn JL (2010) Tuberculosis: what we don’t know can, and does, hurt us. Science 328:852–856PubMedCrossRefGoogle Scholar
  160. 160.
    Saxton K, Baines SD, Freeman J, O’Connor R, Wilcox MH (2008) Effects of exposure of Clostridium difficile PCRF ribotypes 027 and 001 to fluoroquinolones in a human gut model. Antimicrob Agents Chemother 53: 412-420Google Scholar
  161. 161.
    Schaub J, Reuss M (2008) In vivo dynamics of glycolysis in Escherichia coli shows need for growth-rate dependent metabolome analysis. Biotechnol Prog 24:1401–1407CrossRefGoogle Scholar
  162. 162.
    Senior E, Bull AT, Slater JH (1976) Enzyme evolution in a microbial community growing on the herbicide Dalapon. Nature 263:476–479PubMedCrossRefGoogle Scholar
  163. 163.
    Senior PJ (1984) Polyhydroxybutyrate, a speciality polymer of microbial origin. In: Dean ACR, Ellwood DC, Evans CGT (eds) Continuous culture 8: biotechnology, medicine and the environment. Ellis Horwood, Chichester, pp 266–271Google Scholar
  164. 164.
    Shah D, Dang MD, Hasbun R, Koo HL, Jiang ZD, DuPont HL, Garey KW (2010) Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance. Expert Rev Anti Infect Ther 8:555–564PubMedCrossRefGoogle Scholar
  165. 165.
    Shannon SP, Chrzanowski TH, Grover JP (2007) Prey food quality affects flagellate ingestion rates. Microbial Ecol 53:66–73CrossRefGoogle Scholar
  166. 166.
    Shimono N, Morici L, Casal N, Cantrell S, Sidders B, Ehrt S, Riley LW (2003) Hypervirulent mutant of Mycobacterium tuberculosis resulting from disruption of the mce1 operon. Proc Natl Acad Sci U S A 100:15918–15923PubMedCrossRefGoogle Scholar
  167. 167.
    Shockley KR, Scott KL, Conners SB, Johnson MR, Montero CI, Wolfinger RD, Kelly RM (2005) Genome-wide transcriptional variation within and between steady states for continuous growth of the hyperthermophile Thermatoga maritima. Appl Environ Microbiol 71:5572–5576PubMedCrossRefGoogle Scholar
  168. 168.
    Sikyta B (1991) Directed selection of microorganisms in continuous culture. Academia, Prague, pp 1–134Google Scholar
  169. 169.
    Smith SRL (1980) Single cell protein. In: Brenner S, Hartley BS, Rodgers PJ (eds) New horizons in industrial microbiology. The Royal Society, London, pp 63–76Google Scholar
  170. 170.
    Smith VH, Foster BL, Grover JP, Holt RD, Leibold MA, deNoyelles F (2005) Phytoplankton species richness scales consistently from laboratory microcosms to the world’s oceans. Proc Nat Acad Sci USA 102:4393–4396CrossRefGoogle Scholar
  171. 171.
    Snoep JL, Mrwebi M, Schuurmans JM, Rohwer JM, de Mattos MJT (2009) Control of specific growth rate in Saccharomyces cerevisiae. Microbiology 155:1699–1707PubMedCrossRefGoogle Scholar
  172. 172.
    Stejskal A (1966) Fundamental advantages of continuous cultivation of pathogenic microorganisms. In: Malék I, Fencl Z (eds) (1966) Theoretical and methodological basis of continuous culture of microorganisms. Czech Acad Sci, Prague, pp 418–442Google Scholar
  173. 173.
    Sterner RW, Elser JJ (2002) Ecological stoichiometry. Princeton University Press, PrincetonGoogle Scholar
  174. 174.
    Stomp M, van Dijk MA, van Overzee HMJ, Wortel MT, Sigon CAM, Egas M, Hoogveld H, Gons HJ, Huisman J (2008) The timescale of phenotypic plasticity and its impact on competetion in fluctuating environments. American Naturalist 172:E169–E185CrossRefGoogle Scholar
  175. 175.
    Stouthamer AH (1979) The search for correlation between theoretical and experimental growth yields. In: Quayle JR (ed) International review of biochemistry vol 21, microbial biochemistry. University Park Press, Baltimore, pp 1–47Google Scholar
  176. 176.
    Stouthamer AH, Bulthius BA, van Verseveld HW (1990) Energetics of growth at low growth rates and its relevance for the maintenance concept. In: Poole RK, Bazin MJ, Keevil CW (eds) Microbial growth dynamics. IRL, Oxford, pp 85–102Google Scholar
  177. 177.
    Sutherland IW, Ellwood DC (1979) Microbial exopolysaccharides–industrial polymers of current and future potential. In: Bull AT, Ellwood DC, Ratledge C (eds) Microbial technology: current state, future prospects, symposium 29 Soc Gen Microbiol. Cambridge University Press, Cambridge, pp 107–150Google Scholar
  178. 178.
    Tai SL, Daran-Lapujade P, Walsh MC, Pronk JT (2007) Acclimation of Saccharomyces cerevisiae to low temperature: a chemostat-based transcriptome analysis. Mol Biol Cell 18:5100–5112PubMedCrossRefGoogle Scholar
  179. 179.
    Tanji Y, Hattori K, Suzuki K, Miyanaga K (2008) Spontaneous deletion of a 209-kilobase-pair fragment from the Escherichia coli genome occurs with acquisition of resistance to an assortment of infectious phages. Appl Environ Microbiol 74:4256–4263PubMedCrossRefGoogle Scholar
  180. 180.
    Tarantola A (2006) Popper, Bayes and the inverse problem. Nat Phys 2:492–494CrossRefGoogle Scholar
  181. 181.
    Tarkiainen V, Kotiaho T, Mattila I, Virkajarvi L, Aristidou A, Ketola RA (2005) On-line monitoring of continuous beer fermentation process using automatic membrane inlet mass spectrometric system. Talanta 65:1254–1263PubMedCrossRefGoogle Scholar
  182. 182.
    Tempest DW, Herbert D, Phipps PJ (1967) Studies on the growth of Aerobacter aerogenes at low dilution rates in a chemostat. In: Powell EO, Evans CGT, Strange RE, Tempest DW (eds) Continuous culture 3: microbial physiology and continuous culture. Her Majesty’s Stationery Office, London, pp 240–254Google Scholar
  183. 183.
    Tempest DW (1969) Quantitative relationships between inorganic cations and anionic polymers in growing bacteria. In: Meadows PM, Pirt SJ (eds) Microbial growth, symposium 19 Soc Gen Microbiol. Cambridge University Press, Cambridge, pp 87–111Google Scholar
  184. 184.
    Tempest DW, Neijssel OM, Zevenboom W (1983) Properties and performance of microorganisms in laboratory culture: their relevance to growth in natural ecosystems. In: Slater JH, Whittenbury R, Wimpenny JWT (eds) Microbes in their natural environments, symposium 34 Soc Gen Microbiol. Cambridge University Press, Cambridge, pp 119–152Google Scholar
  185. 185.
    Teusink B, Wiersma A, Molenaar D, Francke C, de Vos WM, Siezen RJ, Smid EJ (2006) Analysis of growth of Lactobacillus plantarum WCFS1 on a complex medium using a genome-scale metabolic model. J Biol Chem 281:40041–40048PubMedCrossRefGoogle Scholar
  186. 186.
    Trinci AJP (1994) Evolution of the Quorn® myco-protein fungus, Fusarium graminearum A3/5. Microbiology 140:2181–2188PubMedCrossRefGoogle Scholar
  187. 187.
    van Bodegom P (2007) Microbial maintenance. A critical review on its quantification. Microbial Ecol 53:513–523CrossRefGoogle Scholar
  188. 188.
    van Eunen K, Bouwman J, Daran-Lapujade P, Postmus J, Canelas AB, Mensonides FIC, Orij R, Tuzun I, van den Brink J, Smits JG, van Gulik WM, Brul S, Heijnen JJ, de Winde JH, Teixeira de Mattos MJ, Kettner C, Nielsen J, Westerhoff HV, Bakker BM (2010) Measuring enzyme activities under standardized in vivo-like conditions for systems biology. FEBS J 277:749–760Google Scholar
  189. 189.
    van der Brink J, Akeroyd M, van der Hoeven R, Pronk JT, de Winde JH, Daran-Lapujade P (2009) Energetic limits to metabolic flexibility: responses of Saccharomyces cerevisiae to glucose-galactose transitions. Microbiology 155:1340–1350PubMedCrossRefGoogle Scholar
  190. 190.
    van der Greef J, Martin S, Juhsz P (2007) The art and practice of systems biology in medicine: Mapping patterns of relationships. J Proteome Res 6:1540–1559PubMedCrossRefGoogle Scholar
  191. 191.
    van der Stap I, Vos M, Kooi BW, Mulling BTM, van Donk E, Mooij WM (2009) Algal defenses, population stability, and the risk of herbivore extinctions: a chemostat model and experiment. Ecol Res 24:1145–1153CrossRefGoogle Scholar
  192. 192.
    Veldkamp H, Jannasch HW (1972) Mixed culture studies with the chemostat. J appl Chem Biotechnol 22:105–123CrossRefGoogle Scholar
  193. 193.
    Way JC, Silver PA (2007) Why we need systems biology. Complexity 13:22–29CrossRefGoogle Scholar
  194. 194.
    Weibel DB, DiLuzio WR, Whitesides GM (2007) Microfabrication meets microbiology. Nat Rev Microbiol 5:209–218PubMedCrossRefGoogle Scholar
  195. 195.
    Wecker P, Klockow C, Ellrott A, Quast C, Langhammer P, Harder J, Glöckner FO (2009) Transcriptional response of the model planctomycete Rhodopirellula baltica SHIT to changing environmental conditions. BMC Genomics 10:410–426PubMedCrossRefGoogle Scholar
  196. 196.
    Werner E (2007) All systems go. Nature 446:493–494CrossRefGoogle Scholar
  197. 197.
    Wiebe MG, Robson GD, B, SG, Trinci AJP (1993) Periodic selection in long-term continuous-flow cultures of the filamentous fungus Fusarium graminearum J Gen Microbiol 139: 2811–2817Google Scholar
  198. 198.
    Zeng AP, Sun J (2010) Continuous culture. In: Baltz RH, Demain AL, Davies JE (eds) Manual of industrial microbiology and biotechnology, 3rd edn. ASM, Washington DC, pp 685–699Google Scholar
  199. 199.
    Zhang Z, Boccazzi P, Choi HG, Perozziello G, Sinskey AJ, Jensen KF (2006) Microchemostat–microbial continuous culture in a polmer-based, instrumented microbioreactor. Lab Chip 6:906–913PubMedCrossRefGoogle Scholar
  200. 200.
    Zhong S, Khodursky A, Dykhuizen DE, Dean AM (2004) Evolutionary genomics of ecological specialization. Proc Nat Acad Sci U S A 101:11719–11724CrossRefGoogle Scholar
  201. 201.
    Zhong S, Miller SP, Dykhuisen DE, Dean AM (2009) Transcription, translation, and the evolution of specialists and generalists. Molecular Biol Evol 26:2661–2678CrossRefGoogle Scholar
  202. 202.
    Zilm PS, Bagley CJ, Rogers AH, Milne IR (2007) The proteomic profile of Fusobacterium nucleatum is regulated by growth pH. Microbiology 153:148–159PubMedCrossRefGoogle Scholar
  203. 203.
    Zilm PS, Rogers AH (2007) Co-adhesion and biofilm formation by Fusobacterium nucleatum in response to growth pH. Anaerobe 13:146–152PubMedCrossRefGoogle Scholar

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© Society for Industrial Microbiology 2010

Authors and Affiliations

  1. 1.School of BiosciencesUniversity of KentCanterburyUK

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