Chapter 4 : Division of Labor in Biofilms: the Ecology of Cell Differentiation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Division of Labor in Biofilms: the Ecology of Cell Differentiation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817466/9781555817459_Chap04-1.gif /docserver/preview/fulltext/10.1128/9781555817466/9781555817459_Chap04-2.gif


One of the most remarkable features of the evolutionary process is its capacity to construct. In billions of years a primordial soup of organic compounds evolved to the theater of life extant today. This ability to construct is best illustrated by a number of transitions that have occurred during the natural history of our planet, such as the evolution of the first prebiotic cells, eukaryotes, multicellularity, and eusociality ( ). These transitions all bear a number of striking similarities ( ). First, construction evolves through cooperation ( ). That is, new organizational layers come about through the cooperative interaction of biological units that previously functioned independently. For example, organelles evolved from microbes that engaged in mutualistic interactions through endosymbiosis, and multicellularity evolved from cells that cooperate by sticking together, either via incomplete cell division or through aggregation ( ). In addition to cooperation, a second aspect characterizes major evolutionary transitions: the division of labor ( ). A precise definition of the division of labor will be given below, but one can loosely speak of division of labor when individuals—during their cooperative interactions—specialize in performing different “tasks.” Perhaps the most striking example comes from multicellular development. Multicellular organisms consist of many specialized cell types (e.g., muscle cells, neurons, epithelia, etc.). Despite being genetically identical, these cells have differentiated and thereby organized themselves in different physiological and morphological structures (e.g., organs) that together make up the individual.

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Conceptual and theoretical basis for the division of labor. (A) Growth of cooperative and noncooperative cells when mixed (left) or segregated (right). When mixed, the noncooperative genotype performs better than the cooperative phenotype; it benefits from cooperation without paying the costs. When segregated, the cooperative genotype performs better. (B) Reaction norms. Different colored lines and associated numbers show different types of reaction norms as indicated on the right. (C) Fitness consequences of cell differentiation at the individual level (i.e., cell) and group level (i.e., colony or part of the colony). When cell differentiation is not beneficial at either level, phenotypic heterogeneity is nonadaptive. When it is only beneficial at the cell level, there is cellular specialization. When it is only beneficial at the colony level, there is division of labor. When it is beneficial at both levels, one cannot directly determine the function of cell differentiation.

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Phenotypic trade-offs and the division of labor. Trade-off between two tasks: phenotype A and B. The trade-off constrains a cell such that expressing phenotype A (e.g., photosynthesis) is at the expense of phenotype B (e.g., nitrogen fixation). The trade-off can be weak (concave shape) or strong (convex shape). (A) Expected evolutionary outcome when the trade-off between phenotypes A and B is weak: phenotypic generalist. The regulatory network that controls the expression of phenotypes A and B should result in coexpression. (B) Expected evolutionary outcome when the trade-off between phenotypes A and B is strong: cell specialization and the division of labor. In this case, the regulatory network that controls the expression of phenotypes A and B should result in antagonistic expression and commit cells to a given cell type (positive feedback loops). Consequently, each cell expresses only phenotype A or B.

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Bacterial multicellularity. For each form of multicellularity we show a number of different cell types: green is vegetative cells, blue is spores, and red is terminally differentiated cells, including cells that undergo lysis. (A) Filamentous multicellularity and cell differentiation in cyanobacteria. PatS is a signaling peptide that blocks heterocyst formation in the neighboring cells in the cyanobacteria filaments. (B) Filamentous multicellularity and aerial hyphae formation in actinobacteria. (C) Colonial multicellularity and fruiting body formation in myxobacteria. A-signal-dependent aggregation is illustrated by an arrow, and the level of C-signal is highest in the base and center of a fruiting body.

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

Cell differentiation and pattern formation in biofilms. (A) Simplified scheme of the regulatory circuit that controls cell differentiation. Regulatory repression (red T-bars) or stimulation (green arrows) can involve both transcriptional regulation and (de)phosphorylation. The gray box shows the expected developmental transition in time throughout biofilm formation: motile cells differentiate to matrix-producing cells, which later sporulate. S and S are environmental signals that affect the sensory kinases KinA-E and DegS. (B) Pattern formation in cross-sections and top view of colony biofilms. Cell types shown in cross-sections are sporulating cells (artificially colored yellow or green), motile cells (blue), and matrix-producing cells (red). In the top view, sporulating cells are shown in green and colocalize with the biofilm wrinkles. (C) Feedback between cellular contingency and environmental conditionality. Images are adapted from references and .

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Pattern formation in microcolonies. (A) Fruiting bodies consisting of nonmotile stalk cells (blue) and motile cap cells (yellow). (B) Localization of eDNA in microcolonies (red). (C) Localization of rhamnolipid production (yellow). (D) Live (green) and dead (yellow/red) cells after EDTA treatment in a 4-day-old microcolony. (E) Schematic overview of mushroom-shaped microcolonies and the interaction between the stalk and cap cells through the production of the iron-scavenging siderophore pyoverdine. Images adapted from references , and .

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

Simplified schematic view of the life cycle of biofilm formation. The life cycle is divided into two life phases: the multicellular phase and the dispersal phase. Various environmental conditions influence the switch toward aggregation, typically mediated by a second messenger. When the second messenger passes a certain threshold, aggregation is initiated and, the other way around, when it drops below a certain threshold, cells revert to the dispersal phase.

Citation: van Gestel J, Vlamakis H, Kolter R. 2015. Division of Labor in Biofilms: the Ecology of Cell Differentiation, p 67-97. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0002-2014
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Buss LW . 1987. The Evolution of Individuality. Princeton University Press, Princeton, NJ.
2. Maynard Smith J,, Szathmary E . 1997. The Major Transitions in Evolution. Oxford University Press, Oxford, UK.
3. Nowak MA . 2006. Five rules for the evolution of cooperation. Science 314 : 15601563.[PubMed] [CrossRef]
4. Michod RE,, Herron MD . 2006. Cooperation and conflict during evolutionary transitions in individuality. J Evol Biol 19 : 14061409.[PubMed] [CrossRef]
5. Grosberg RK,, Strathmann RR . 2007. The evolution of multicellularity: a minor major transition? Annu Rev Ecol Evol Syst 38 : 621654.[CrossRef]
6. Nowak MA,, Tarnita CE,, Antal T . 2010. Evolutionary dynamics in structured populations. Philos Trans R Soc B Biol Sci 365 : 1930.[PubMed] [CrossRef]
7. Tarnita CE,, Taubes CH,, Nowak MA . 2013. Evolutionary construction by staying together and coming together. J Theor Biol 320 : 1022.[PubMed] [CrossRef]
8. Kirk DL . 2005. A twelve-step program for evolving multicellularity and a division of labor. Bioessays 27 : 299310.[PubMed] [CrossRef]
9. Michod RE . 2007. Evolution of individuality during the transition from unicellular to multicellular life. Proc Natl Acad Sci USA 104 : 86138618.[PubMed] [CrossRef]
10. Pepper JW,, Herron MD . 2008. Does biology need an organism concept? Biol Rev Camb Philos Soc 83 : 621627.[PubMed] [CrossRef]
11. Herron MD,, Rashidi A,, Shelton DE,, Driscoll WW . 2013. Cellular differentiation and individuality in the “minor” multicellular taxa. Biol Rev 88 : 844861.[PubMed] [CrossRef]
12. Watnick P,, Kolter R . 2000. Biofilm, city of microbes. J Bacteriol 182 : 26752679.[PubMed] [CrossRef]
13. Nadell CD,, Xavier JB,, Foster KR . 2009. The sociobiology of biofilms. FEMS Microbiol Rev 33 : 206224.[PubMed] [CrossRef]
14. Monds RD,, O’Toole GA . 2009. The developmental model of microbial biofilms: ten years of a paradigm up for review. Trends Microbiol 17 : 7387.[PubMed] [CrossRef]
15. Griffin AS,, West SA,, Buckling A . 2004. Cooperation and competition in pathogenic bacteria. Nature 430 : 10241027.[PubMed] [CrossRef]
16. West SA,, Griffin AS,, Gardner A,, Diggle SP . 2006. Social evolution theory for microorganisms. Nat Rev Microbiol 4 : 597607.[PubMed] [CrossRef]
17. Fletcher JA,, Doebeli M . 2009. A simple and general explanation for the evolution of altruism. Proc R Soc B Biol Sci 276 : 1319.[PubMed] [CrossRef]
18. Nowak MA,, Sigmund K . 1992. Tit for tat in heterogeneous populations. Nature 355 : 250253.[CrossRef]
19. Nowak MA,, Bonhoeffer S,, May RM . 1994. Spatial games and the maintenance of cooperation. Proc Natl Acad Sci USA 91 : 48774881.[PubMed] [CrossRef]
20. Kreft JU . 2004. Biofilms promote altruism. Microbiology 150 : 27512760.[PubMed] [CrossRef]
21. Xavier JB,, Foster KR . 2007. Cooperation and conflict in microbial biofilms. Proc Natl Acad Sci USA 104 : 876881.[PubMed] [CrossRef]
22. Timmis JN,, Ayliffe MA,, Huang CY,, Martin W . 2004. Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet 5 : 123135.[PubMed] [CrossRef]
23. Wernegreen JJ . 2004. Endosymbiosis: lessons in conflict resolution. PLoS Biol 2 : e68. doi:10.1371/journal.pbio.0020068. [PubMed] [CrossRef]
24. Husnik F,, Nikoh N,, Koga R,, Ross L,, Duncan RP,, Fujie M,, Tanaka M,, Satoh N,, Bachtrog D,, Wilson ACC,, von Dohlen CD,, Fukatsu T,, McCutcheon JP . 2013. Horizontal gene transfer from diverse bacteria to an insect genome enables a tripartite nested mealybug symbiosis. Cell 153 : 15671578.[PubMed] [CrossRef]
25. Schlichting CD,, Pigliucci M . 1998. Phenotypic Evolution: A Reaction Norm Perspective. Sinauer, Sunderland, MA.
26. Beldade P,, Mateus ARA,, Keller RA . 2011. Evolution and molecular mechanisms of adaptive developmental plasticity. Mol Ecol 20 : 13471363.[PubMed] [CrossRef]
27. Schlichting CD . 2003. Origins of differentiation via phenotypic plasticity. Evol Dev 5 : 98105.[PubMed] [CrossRef]
28. Smits WK,, Kuipers OP,, Veening JW . 2006. Phenotypic variation in bacteria: the role of feedback regulation. Nat Rev Microbiol 4 : 259271.[PubMed] [CrossRef]
29. Alon U . 2007. Network motifs: theory and experimental approaches. Nat Rev Genet 8 : 450461.[PubMed] [CrossRef]
30. Dubnau D,, Losick R . 2006. Bistability in bacteria. Mol Microbiol 61 : 564572.[PubMed] [CrossRef]
31. Mitrophanov AY,, Groisman EA . 2008. Positive feedback in cellular control systems. BioEssays 30 : 542555.[PubMed] [CrossRef]
32. Guttenplan SB,, Kearns DB . 2013. Regulation of flagellar motility during biofilm formation. FEMS Microbiol Rev 37 : 849871.[PubMed] [CrossRef]
33. Duarte A,, Weissing FJ,, Pen I,, Keller L . 2011. An evolutionary perspective on self-organized division of labor in social insects. Annu Rev Ecol Evol Syst 42 : 91110.[CrossRef]
34. Meier P,, Finch A,, Evan G . 2000. Apoptosis in development. Nature 407 : 796801.[PubMed] [CrossRef]
35. Ameisen JC . 2002. On the origin, evolution, and nature of programmed cell death: a timeline of four billion years. Cell Death Differ 9 : 367393.[PubMed] [CrossRef]
36. Golstein P,, Aubry L,, Levraud JP . 2003. Cell-death alternative model organisms: why and which? Nat Rev Mol Cell Biol 4 : 798807.[PubMed] [CrossRef]
37. Engelberg-Kulka H,, Amitai S,, Kolodkin-Gal I,, Hazan R . 2006. Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet 2 : e135. doi:10.1371/journal.pgen.0020135. [PubMed] [CrossRef]
38. Claverys JP,, Havarstein LS . 2007. Cannibalism and fratricide: mechanisms and raisons d’etre. Nat Rev Microbiol 5 : 219229.[PubMed] [CrossRef]
39. Schopf JW . 1993. Microfossils of the Early Archean Apex Chert: new evidence of the antiquity of life. Science 260 : 640646.[PubMed] [CrossRef]
40. Knoll AH . 2011. The multiple origins of complex multicellularity. Annu Rev Earth Planet Sci 39 : 217239.[CrossRef]
41. Adams DG,, Duggan PS . 1999. Heterocyst and akinete differentiation in cyanobacteria. New Phytol 144 : 333.[CrossRef]
42. Flores E,, Herrero A . 2010. Compartmentalized function through cell differentiation in filamentous cyanobacteria. Nat Rev Microbiol 8 : 3950.[PubMed] [CrossRef]
43. Schirrmeister BE,, de Vos JM,, Antonelli A,, Bagheri HC . 2013. Evolution of multicellularity coincided with increased diversification of cyanobacteria and the Great Oxidation Event. Proc Natl Acad Sci USA 110 : 17911796.[PubMed] [CrossRef]
44. Wolk CP . 1968. Movement of carbon from vegetative cells to heterocysts in Anabaena cylindrica . J Bacteriol 96 : 21382143.[PubMed]
45. Wolk CP,, Thomas J,, Shaffer PW,, Austin SM,, Galonsky A . 1976. Pathway of nitrogen metabolism after fixation of 13N-labeled nitrogen gas by the cyanobacterium, Anabaena cylindrica . J Biol Chem 251 : 50275034.[PubMed]
46. Frías JE,, Flores E,, Herrero A . 1994. Requirement of the regulatory protein NtcA for the expression of nitrogen assimilation and heterocyst development genes in the cyanobacterium Anabaena sp. PCC7120. Mol Microbiol 14 : 823832.[PubMed] [CrossRef]
47. Black TA,, Cai Y,, Wolk CP . 1993. Spatial expression and autoregulation of hetR, a gene involved in the control of heterocyst development in Anabaena . Mol Microbiol 9 : 7784.[PubMed] [CrossRef]
48. Yoon HS,, Golden JW . 1998. Heterocyst pattern formation controlled by a diffusible peptide. Science 282 : 935938.[PubMed] [CrossRef]
49. Callahan SM,, Buikema WJ . 2001. The role of HetN in maintenance of the heterocyst pattern in Anabaena sp. PCC 7120. Mol Microbiol 40 : 941950.[PubMed] [CrossRef]
50. Yoon HS,, Golden JW . 2001. PatS and products of nitrogen fixation control heterocyst pattern. J Bacteriol 183 : 26052613.[PubMed] [CrossRef]
51. Zhang CC,, Laurent S,, Sakr S,, Peng L,, Bédu S . 2006. Heterocyst differentiation and pattern formation in cyanobacteria: a chorus of signals. Mol Microbiol 59 : 367375.[PubMed] [CrossRef]
52. Rossetti V,, Schirrmeister BE,, Bernasconi MV,, Bagheri HC . 2010. The evolutionary path to terminal differentiation and division of labor in cyanobacteria. J Theor Biol 262 : 2334.[PubMed] [CrossRef]
53. Matias Rodrigues JF,, Rankin DJ,, Rossetti V,, Wagner A,, Bagheri HC . 2012. Differences in cell division rates drive the evolution of terminal differentiation in microbes. PLoS Comput Biol 8 : e1002468. doi:10.1371/journal.pcbi.1002468. [PubMed] [CrossRef]
54. Misra HS,, Tuli R . 2000. Differential expression of photosynthesis and nitrogen fixation genes in the cyanobacterium Plectonema boryanum . Plant Physiol 122 : 731736.[PubMed] [CrossRef]
55. Tomitani A,, Knoll AH,, Cavanaugh CM,, Ohno T . 2006. The evolutionary diversification of cyanobacteria: molecular–phylogenetic and paleontological perspectives. Proc Natl Acad Sci USA 103 : 54425447.[PubMed] [CrossRef]
56. Michod RE,, Viossat Y,, Solari CA,, Hurand M,, Nedelcu AM . 2006. Life-history evolution and the origin of multicellularity. J Theor Biol 239 : 257272.[PubMed] [CrossRef]
57. Michod RE . 2006. The group covariance effect and fitness trade-offs during evolutionary transitions in individuality. Proc Natl Acad Sci USA 103 : 91139117.[PubMed] [CrossRef]
58. Flärdh K,, Buttner MJ . 2009. Streptomyces morphogenetics: dissecting differentiation in a filamentous bacterium. Nat Rev Microbiol 7 : 3649.[PubMed] [CrossRef]
59. McCormick JR,, Flärdh K . 2012. Signals and regulators that govern Streptomyces development. FEMS Microbiol Rev 36 : 206231.[PubMed] [CrossRef]
60. Kang SG,, Lee KJ . 1997. Kinetic analysis of morphological differentiation and protease production in Streptomyces albidoflavus SMF301. Microbiology 143 : 27092714.[CrossRef]
61. Chater KF,, Biró S,, Lee KJ,, Palmer T,, Schrempf H . 2010. The complex extracellular biology of Streptomyces . FEMS Microbiol Rev 34 : 171198.[PubMed] [CrossRef]
62. Wildermuth H . 1970. Development and organization of the aerial mycelium in Streptomyces coelicolor . J Gen Microbiol 60 : 4350.[PubMed] [CrossRef]
63. Miguélez EM,, Hardisson C,, Manzanal MB . 1999. Hyphal death during colony development in Streptomyces antibioticus: morphological evidence for the existence of a process of cell deletion in a multicellular prokaryote. J Cell Biol 145 : 515525.[PubMed] [CrossRef]
64. Manteca A,, Claessen D,, Lopez-Iglesias C,, Sanchez J . 2007. Aerial hyphae in surface cultures of Streptomyces lividans and Streptomyces coelicolor originate from viable segments surviving an early programmed cell death event. FEMS Microbiol Lett 274 : 118125.[PubMed] [CrossRef]
65. Stewart PS . 2003. Diffusion in biofilms. J Bacteriol 185 : 14851491.[PubMed] [CrossRef]
66. Rani SA,, Pitts B,, Beyenal H,, Veluchamy RA,, Lewandowski Z,, Davison WM,, Buckingham-Meyer K,, Stewart PS . 2007. Spatial patterns of DNA replication, protein synthesis, and oxygen concentration within bacterial biofilms reveal diverse physiological states. J Bacteriol 189 : 42234233.[PubMed] [CrossRef]
67. Stewart PS,, Franklin MJ . 2008. Physiological heterogeneity in biofilms. Nat Rev Microbiol 6 : 199210.[PubMed] [CrossRef]
68. Kolter R,, Greenberg EP . 2006. Microbial sciences: the superficial life of microbes. Nature 441 : 300302.[PubMed] [CrossRef]
69. Wolpert L . 1969. Positional information and the spatial pattern of cellular differentiation. J Theor Biol 25 : 147.[PubMed] [CrossRef]
70. Wolpert L,, Beddington R,, Jessell T,, Lawrence P,, Meyerowitz E,, Smith J . 2002. Principles of Development. Oxford University Press, New York.
71. Berleman J,, Auer M . 2013. The role of bacterial outer membrane vesicles for intra- and interspecies delivery. Environ Microbiol 15 : 347354.[PubMed] [CrossRef]
72. Konovalova A,, Petters T,, Søgaard-Andersen L . 2010. Extracellular biology of Myxococcus xanthus . FEMS Microbiol Rev 34 : 89106.[PubMed] [CrossRef]
73. Higgs PI,, Hartzell PL,, Holkenbrink C,, Hoiczyk E, . 2014. Myxococcus xanthus vegetative and developmental cell heterogeneity. In Yang Z,, Higgs PI (ed), Myxobacteria: Genomics and Molecular Biology. Horizon Scientific Press, Norfolk, UK.
74. O’Toole G,, Kaplan HB,, Kolter R . 2000. Biofilm formation as microbial development. Annu Rev Microbiol 54 : 4979.[PubMed] [CrossRef]
75. Kaiser D . 2001. Building a multicellular organism. Annu Rev Genet 35 : 103123.[PubMed] [CrossRef]
76. Pathak DT,, Wei X,, Wall D . 2012. Myxobacterial tools for social interactions. Res Microbiol 163 : 579591.[PubMed] [CrossRef]
77. Julien B,, Kaiser AD,, Garza A . 2000. Spatial control of cell differentiation in Myxococcus xanthus . Proc Natl Acad Sci USA 97 : 90989103.[PubMed] [CrossRef]
78. Lee B,, Holkenbrink C,, Treuner-Lange A,, Higgs PI . 2012. Myxococcus xanthus developmental cell fate production: heterogeneous accumulation of developmental regulatory proteins and reexamination of the role of MazF in developmental lysis. J Bacteriol 194 : 30583068.[PubMed] [CrossRef]
79. O’Connor KA,, Zusman DR . 1991. Development in Myxococcus xanthus involves differentiation into two cell types, peripheral rods and spores. J Bacteriol 173 : 33183333.[PubMed]
80. Hoiczyk E,, Ring MW,, McHugh CA,, Schwär G,, Bode E,, Krug D,, Altmeyer MO,, Lu JZ,, Bode HB . 2009. Lipid body formation plays a central role in cell fate determination during developmental differentiation of Myxococcus xanthus . Mol Microbiol 74 : 497517.[PubMed] [CrossRef]
81. Kuspa A,, Plamann L,, Kaiser D . 1992. A-signalling and the cell density requirement for Myxococcus xanthus development. J Bacteriol 174 : 73607369.[PubMed]
82. Kaiser D . 2004. Signaling in myxobacteria. Annu Rev Microbiol 58 : 7598.[PubMed] [CrossRef]
83. Lobedanz S,, Søgaard-Andersen L . 2003. Identification of the C-signal, a contact-dependent morphogen coordinating multiple developmental responses in Myxococcus xanthus . Genes Dev 17 : 21512161.[PubMed] [CrossRef]
84. Kroos L . 2007. The Bacillus and Myxococcus developmental networks and their transcriptional regulators. Annu Rev Genet 41 : 1339.[PubMed] [CrossRef]
85. Spröer C,, Reichenbach H,, Stackebrandt E . 1999. The correlation between morphological and phylogenetic classification of myxobacteria. Int J Syst Bacteriol 49 : 12551262.[PubMed] [CrossRef]
86. Nariya H,, Inouye M . 2008. MazF, an mRNA interferase, mediates programmed cell death during multicellular Myxococcus development. Cell 132 : 5566.[PubMed] [CrossRef]
87. Velicer GJ,, Vos M . 2009. Sociobiology of the Myxobacteria . Annu Rev Microbiol 63 : 599623.[PubMed] [CrossRef]
88. Hagen DC,, Bretscher AP,, Kaiser D . 1978. Synergism between morphogenetic mutants of Myxococcus xanthus . Dev Biol 64 : 284296.[PubMed] [CrossRef]
89. Kroos L,, Kaiser D . 1987. Expression of many developmentally regulated genes in Myxococcus depends on a sequence of cell interactions. Genes Dev 1 : 840854.[PubMed] [CrossRef]
90. Velicer GJ,, Kroos L,, Lenski RE . 2000. Developmental cheating in the social bacterium Myxococcus xanthus . Nature 404 : 598601.[PubMed] [CrossRef]
91. Fiegna F,, Velicer GJ . 2003. Competitive fates of bacterial social parasites: persistence and self-induced extinction of Myxococcus xanthus cheaters. Proc R Soc Lond Ser B Biol Sci 270 : 15271534.[PubMed] [CrossRef]
92. Fiegna F,, Velicer GJ . 2005. Exploitative and hierarchical antagonism in a cooperative bacterium. PloS Biol 3 : 19801987.[PubMed] [CrossRef]
93. Fiegna F,, Yu YTN,, Kadam SV,, Velicer GJ . 2006. Evolution of an obligate social cheater to a superior cooperator. Nature 441 : 310314.[PubMed] [CrossRef]
94. Vos M,, Velicer GJ . 2009. Social conflict in centimeter and global-scale populations of the bacterium Myxococcus xanthus . Curr Biol 19 : 17631767.[PubMed] [CrossRef]
95. Velicer GJ,, Kroos L,, Lenski RE . 1998. Loss of social behaviors by Myxococcus xanthus during evolution in an unstructured habitat. Proc Natl Acad Sci USA 95 : 1237612380.[PubMed] [CrossRef]
96. Veening JW,, Smits WK,, Kuipers OP . 2008. Bistability, epigenetics, and bet-hedging in bacteria. Annu Rev Microbiol 62 : 193210.[PubMed] [CrossRef]
97. Lopez D,, Vlamakis H,, Kolter R . 2009. Generation of multiple cell types in Bacillus subtilis . FEMS Microbiol Rev 33 : 152163.[PubMed] [CrossRef]
98. Marlow VL,, Cianfanelli FR,, Porter M,, Cairns LS,, Dale JK,, Stanley-Wall NR . 2014. The prevalence and origin of exoprotease-producing cells in the Bacillus subtilis biofilm. Microbiology 160 : 5666.[PubMed] [CrossRef]
99. Kearns DB,, Losick R . 2005. Cell population heterogeneity during growth of Bacillus subtilis . Genes Dev 19 : 30833094.[PubMed] [CrossRef]
100. Blair KM,, Turner L,, Winkelman JT,, Berg HC,, Kearns DB . 2008. A molecular clutch disables flagella in the Bacillus subtilis biofilm. Science 320 : 16361638.[PubMed] [CrossRef]
101. Nakano MM,, Magnuson R,, Myers A,, Curry J,, Grossman AD,, Zuber P . 1991. srfA is an operon required for surfactin production, competence development, and efficient sporulation in Bacillus subtilis . J Bacteriol 173 : 17701778.[PubMed]
102. Nakano MM,, Xia LA,, Zuber P . 1991. Transcription initiation of the srfA operon, which is controlled by the ComP-ComA signal transduction system in Bacillus subtilis . J Bacteriol 173 : 54875493.[PubMed]
103. Branda SS,, González-Pastor JE,, Ben-Yehuda S,, Losick R,, Kolter R . 2001. Fruiting body formation by Bacillus subtilis . Proc Natl Acad Sci USA 98 : 1162111626.[PubMed] [CrossRef]
104. Lopez D,, Fischbach MA,, Chu F,, Losick R,, Kolter R . 2009. Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis . Proc Natl Acad Sci USA 106 : 280285.[PubMed] [CrossRef]
105. Lopez D,, Vlamakis H,, Losick R,, Kolter R . 2009. Paracrine signaling in a bacterium. Genes Dev 23 : 16311638.[PubMed] [CrossRef]
106. Bais HP,, Fall R,, Vivanco JM . 2004. Biocontrol of Bacillus subtilis against infection of Arabidopsis roots by Pseudomonas syringae is facilitated by biofilm formation and surfactin production. Plant Physiol 134 : 307319.[PubMed] [CrossRef]
107. Gonzalez DJ,, Haste NM,, Hollands A,, Fleming TC,, Hamby M,, Pogliano K,, Nizet V,, Dorrestein PC . 2011. Microbial competition between Bacillus subtilis and Staphylococcus aureus monitored by imaging mass spectrometry. Microbiology 157 : 24852492.[PubMed] [CrossRef]
108. Branda SS,, González-Pastor JE,, Dervyn E,, Ehrlich SD,, Losick R,, Kolter R . 2004. Genes involved in formation of structured multicellular communities by Bacillus subtilis . J Bacteriol 186 : 39703979.[PubMed] [CrossRef]
109. Branda SS,, Chu F,, Kearns DB,, Losick R,, Kolter R . 2006. A major protein component of the Bacillus subtilis biofilm matrix. Mol Microbiol 59 : 12291238.[PubMed] [CrossRef]
110. Marvasi M,, Visscher PT,, Casillas Martinez L . 2010. Exopolymeric substances (EPS) from Bacillus subtilis: polymers and genes encoding their synthesis. FEMS Microbiol Lett 313 : 19.[PubMed] [CrossRef]
111. Romero D,, Aguilar C,, Losick R,, Kolter R . 2010. Amyloid fibers provide structural integrity to Bacillus subtilis biofilms. Proc Natl Acad Sci USA 107 : 22302234.[PubMed] [CrossRef]
112. Romero D,, Vlamakis H,, Losick R,, Kolter R . 2011. An accessory protein required for anchoring and assembly of amyloid fibres in B. subtilis biofilms. Mol Microbiol 80 : 11551168.[CrossRef]
113. Verhamme DT,, Murray EJ,, Stanley-Wall NR . 2009. DegU and Spo0A jointly control transcription of two loci required for complex colony development by Bacillus subtilis . J Bacteriol 191 : 100108.[PubMed] [CrossRef]
114. Kovács ÁT,, van Gestel J,, Kuipers OP . 2012. The protective layer of biofilm: a repellent function for a new class of amphiphilic proteins. Mol Microbiol 85 : 811.[PubMed] [CrossRef]
115. Kobayashi K,, Iwano M . 2012. BslA (YuaB) forms a hydrophobic layer on the surface of Bacillus subtilis biofilms. Mol Microbiol 85 : 5166.[PubMed] [CrossRef]
116. Hobley L,, Ostrowski A,, Rao FV,, Bromley KM,, Porter M,, Prescott AR,, MacPhee CE,, van Aalten DMF,, Stanley-Wall NR . 2013. BslA is a self-assembling bacterial hydrophobin that coats the Bacillus subtilis biofilm. Proc Natl Acad Sci USA 110 : 1360013605.[PubMed] [CrossRef]
117. Gonzalez-Pastor JE,, Hobbs EC,, Losick R . 2003. Cannibalism by sporulating bacteria. Science 301 : 510513.[PubMed] [CrossRef]
118. Ellermeier CD,, Hobbs EC,, Gonzalez-Pastor JE,, Losick R . 2006. A three-protein signaling pathway governing immunity to a bacterial cannibalism toxin. Cell 124 : 549559.[PubMed] [CrossRef]
119. Lopez D,, Vlamakis H,, Losick R,, Kolter R . 2009. Cannibalism enhances biofilm development in Bacillus subtilis . Mol Microbiol 74 : 609618.[PubMed] [CrossRef]
120. Nandy SK,, Bapat PM,, Venkatesh KV . 2007. Sporulating bacteria prefers predation to cannibalism in mixed cultures. FEBS Lett 581 : 151156.[PubMed] [CrossRef]
121. Msadek T . 1999. When the going gets tough: survival strategies and environmental signaling networks in Bacillus subtilis . Trends Microbiol 7 : 201207.[PubMed] [CrossRef]
122. Veening JW,, Igoshin OA,, Eijlander RT,, Nijland R,, Hamoen LW,, Kuipers OP . 2008. Transient heterogeneity in extracellular protease production by Bacillus subtilis . Mol Syst Biol 4 : 184. [PubMed] [CrossRef]
123. Eichenberger P,, Fujita M,, Jensen ST,, Conlon EM,, Rudner DZ,, Wang ST,, Ferguson C,, Haga K,, Sato T,, Liu JS,, Losick R . 2004. The program of gene transcription for a single differentiating cell type during sporulation in Bacillus subtilis . PLoS Biol 2 : 16641683.[PubMed] [CrossRef]
124. Piggot PJ,, Hilbert DW . 2004. Sporulation of Bacillus subtilis . Curr Opin Microbiol 7 : 579586.[PubMed] [CrossRef]
125. Dworkin J,, Losick R . 2005. Developmental commitment in a bacterium. Cell 121 : 401409.[PubMed] [CrossRef]
126. Chai YR,, Chu F,, Kolter R,, Losick R . 2008. Bistability and biofilm formation in Bacillus subtilis . Mol Microbiol 67 : 254263.[PubMed] [CrossRef]
127. Murray EJ,, Kiley TB,, Stanley-Wall NR . 2009. A pivotal role for the response regulator DegU in controlling multicellular behaviour. Microbiology 155 : 18.[PubMed] [CrossRef]
128. Vlamakis H,, Chai Y,, Beauregard P,, Losick R,, Kolter R . 2013. Sticking together: building a biofilm the Bacillus subtilis way. Nat Rev Microbiol 11 : 157168.[PubMed] [CrossRef]
129. Hamon MA,, Lazazzera BA . 2001. The sporulation transcription factor Spo0A is required for biofilm development in Bacillus subtilis . Mol Microbiol 42 : 11991209.[PubMed] [CrossRef]
130. Fujita M,, Gonzalez-Pastor JE,, Losick R . 2005. High- and low-threshold genes in the Spo0A regulon of Bacillus subtilis . J Bacteriol 187 : 13571368.[PubMed] [CrossRef]
131. Molle V,, Fujita M,, Jensen ST,, Eichenberger P,, González-Pastor JE,, Liu JS,, Losick R . 2003. The Spo0A regulon of Bacillus subtilis . Mol Microbiol 50 : 16831701.[PubMed] [CrossRef]
132. Verhamme DT,, Kiley TB,, Stanley-Wall NR . 2007. DegU co-ordinates multicellular behaviour exhibited by Bacillus subtilis . Mol Microbiol 65 : 554568.[PubMed] [CrossRef]
133. Jiang M,, Shao WL,, Perego M,, Hoch JA . 2000. Multiple histidine kinases regulate entry into stationary phase and sporulation in Bacillus subtilis . Mol Microbiol 38 : 535542.[PubMed] [CrossRef]
134. McLoon AL,, Kolodkin-Gal I,, Rubinstein SM,, Kolter R,, Losick R . 2011. Spatial regulation of histidine kinases governing biofilm formation in Bacillus subtilis . J Bacteriol 193 : 679685.[PubMed] [CrossRef]
135. Aguilar C,, Vlamakis H,, Guzman A,, Losick R,, Kolter R . 2010. KinD is a checkpoint protein linking spore formation to extracellular-matrix production in Bacillus subtilis biofilms. MBio 1 : 17. doi:10.1128/mBio.00035-10.
136. Lopez D,, Kolter R . 2010. Extracellular signals that define distinct and coexisting cell fates in Bacillus subtilis . FEMS Microbiol Rev 34 : 134149.[PubMed] [CrossRef]
137. Shank EA,, Klepac-Ceraj V,, Collado-Torres L,, Powers GE,, Losick R,, Kolter R . 2011. Interspecies interactions that result in Bacillus subtilis forming biofilms are mediated mainly by members of its own genus. Proc Natl Acad Sci USA 108 : E1236E1243.[PubMed] [CrossRef]
138. Kolodkin-Gal I,, Elsholz AKW,, Muth C,, Girguis PR,, Kolter R,, Losick R . 2013. Respiration control of multicellularity in Bacillus subtilis by a complex of the cytochrome chain with a membrane-embedded histidine kinase. Genes Dev 27 : 887899.[PubMed] [CrossRef]
139. Bai U,, Mandic-Mulec I,, Smith I . 1993. SinI modulates the activity of SinR, a developmental switch protein of Bacillus subtilis, by protein-protein interaction. Genes Dev 7 : 139148.[PubMed] [CrossRef]
140. Lewis RJ,, Brannigana JA,, Smith I,, Wilkinson AJ . 1996. Crystallisation of the Bacillus subtilis sporulation inhibitor SinR, complexed with its antagonist, Sinl. FEBS Lett 378 : 98100.[PubMed] [CrossRef]
141. Kearns DB,, Chu F,, Branda SS,, Kolter R,, Losick R . 2004. A master regulator for biofilm formation by Bacillus subtilis . Mol Microbiol 55 : 739749.[PubMed] [CrossRef]
142. Winkelman JT,, Bree AC,, Bate AR,, Eichenberger P,, Gourse RL,, Kearns DB . 2013. RemA is a DNA-binding protein that activates biofilm matrix gene expression in Bacillus subtilis . Mol Microbiol 88 : 984997.[PubMed] [CrossRef]
143. Hamon MA,, Stanley NR,, Britton RA,, Grossman AD,, Lazazzera BA . 2004. Identification of AbrB-regulated genes involved in biofilm formation by Bacillus subtilis . Mol Microbiol 52 : 847860.[PubMed] [CrossRef]
144. Veening JW,, Kuipers OP,, Brul S,, Hellingwerf KJ,, Kort R . 2006. Effects of phosphorelay perturbations on architecture, sporulation, and spore resistance in biofilms of Bacillus subtilis . J Bacteriol 188 : 30993109.[PubMed] [CrossRef]
145. Chu F,, Kearns DB,, McLoon A,, Chai Y,, Kolter R,, Losick R . 2008. A novel regulatory protein governing biofilm formation in Bacillus subtilis . Mol Microbiol 68 : 11171127.[PubMed] [CrossRef]
146. Kobayashi K . 2008. SlrR/SlrA controls the initiation of biofilm formation in Bacillus subtilis . Mol Microbiol 69 : 13991410.[PubMed] [CrossRef]
147. Chai Y,, Kolter R,, Losick R . 2009. Paralogous antirepressors acting on the master regulator for biofilm formation in Bacillus subtilis . Mol Microbiol 74 : 876887.[PubMed] [CrossRef]
148. Norman TM,, Lord ND,, Paulsson J,, Losick R . 2013. Memory and modularity in cell-fate decision making. Nature 503 : 481486.[PubMed] [CrossRef]
149. Chai Y,, Norman T,, Kolter R,, Losick R . 2011. Evidence that metabolism and chromosome copy number control mutually exclusive cell fates in Bacillus subtilis . EMBO J 30 : 14021413.[PubMed] [CrossRef]
150. Davidson CJ,, Surette MG . 2008. Individuality in bacteria. Annu Rev Genet 42 : 253268.[PubMed] [CrossRef]
151. Eldar A,, Elowitz MB . 2010. Functional roles for noise in genetic circuits. Nature 467 : 167173.[PubMed] [CrossRef]
152. Losick R,, Desplan C . 2008. Stochasticity and cell fate. Science 320 : 6568.[PubMed] [CrossRef]
153. Veening JW,, Stewart EJ,, Berngruber TW,, Taddei F,, Kuipers OP,, Hamoen LW . 2008. Bet-hedging and epigenetic inheritance in bacterial cell development. Proc Natl Acad Sci USA 105 : 43934398.[PubMed] [CrossRef]
154. Süel GM,, Garcia-Ojalvo J,, Liberman LM,, Elowitz MB . 2006. An excitable gene regulatory circuit induces transient cellular differentiation. Nature 440 : 545550.[PubMed] [CrossRef]
155. Maamar H,, Raj A,, Dubnau D . 2007. Noise in gene expression determines cell fate in Bacillus subtilis . Science 317 : 526529.[PubMed] [CrossRef]
156. Süel GM,, Kulkarni RP,, Dworkin J,, Garcia-Ojalvo J,, Elowitz MB . 2007. Tunability and noise dependence in differentiation dynamics. Science 315 : 17161719.[PubMed] [CrossRef]
157. Çağatay T,, Turcotte M,, Elowitz MB,, Garcia-Ojalvo J,, Süel GM . 2009. Architecture-dependent noise discriminates functionally analogous differentiation circuits. Cell 139 : 512522.[PubMed] [CrossRef]
158. Chai Y,, Norman T,, Kolter R,, Losick R . 2010. An epigenetic switch governing daughter cell separation in Bacillus subtilis . Genes Dev 24 : 754765.[PubMed] [CrossRef]
159. Chai Y,, Kolter R,, Losick R . 2010. Reversal of an epigenetic switch governing cell chaining in Bacillus subtilis by protein instability. Mol Microbiol 78 : 218229.[PubMed] [CrossRef]
160. Seger J . 1987. What is bet-hedging? Oxf Surv Evol Biol 4 : 182211.
161. Kussell E,, Leibler S . 2005. Phenotypic diversity, population growth, and information in fluctuating environments. Science 309 : 20752078.[PubMed] [CrossRef]
162. De Jong IG,, Haccou P,, Kuipers OP . 2011. Bet hedging or not? A guide to proper classification of microbial survival strategies. Bioessays 33 : 215223.[PubMed] [CrossRef]
163. Balaban NQ,, Merrin J,, Chait R,, Kowalik L,, Leibler S . 2004. Bacterial persistence as a phenotypic switch. Science 305 : 16221625.[PubMed] [CrossRef]
164. Thattai M,, van Oudenaarden A . 2004. Stochastic gene expression in fluctuating environments. Genetics 167 : 523530.[PubMed] [CrossRef]
165. Donaldson-Matasci MC,, Lachmann M,, Bergstrom CT . 2008. Phenotypic diversity as an adaptation to environmental uncertainty. Evol Ecol Res 10 : 493515.
166. Frank SA . 2011. Natural selection. I. Variable environments and uncertain returns on investment. J Evol Biol 24 : 22992309.[PubMed] [CrossRef]
167. Starrfelt J,, Kokko H . 2012. Bet-hedging: a triple trade-off between means, variances and correlations. Biol Rev 87 : 742755.[PubMed] [CrossRef]
168. Maamar H,, Dubnau D . 2005. Bistability in the Bacillus subtilis K-state (competence) system requires a positive feedback loop. Mol Microbiol 56 : 615624.[PubMed] [CrossRef]
169. Vlamakis H,, Aguilar C,, Losick R,, Kolter R . 2008. Control of cell fate by the formation of an architecturally complex bacterial community. Genes Dev 22 : 945953.[PubMed] [CrossRef]
170. Bonner JT . 2001. First Signals: the Evolution of Multicellular Development. Princeton University Press, Princeton, NJ.
171. Ostrowski A,, Mehert A,, Prescott A,, Kiley TB,, Stanley-Wall NR . 2011. YuaB functions synergistically with the exopolysaccharide and TasA amyloid fibers to allow biofilm formation by Bacillus subtilis . J Bacteriol 193 : 48214831.[PubMed] [CrossRef]
172. Beauregard PB,, Chai Y,, Vlamakis H,, Losick R,, Kolter R . 2013. Bacillus subtilis biofilm induction by plant polysaccharides. Proc Natl Acad Sci USA 110 : E1621E1630.[PubMed] [CrossRef]
173. Asally M,, Kittisopikul M,, Rué P,, Du Y,, Hu Z,, Cagatay T,, Robinson AB,, Lu H,, Garcia-Ojalvo J,, Süel GM . 2012. Localized cell death focuses mechanical forces during 3D patterning in a biofilm. Proc Natl Acad Sci USA 109 : 1889118896.[PubMed] [CrossRef]
174. Webb JS,, Thompson LS,, James S,, Charlton T,, Tolker-Nielsen T,, Koch B,, Givskov M,, Kjelleberg S . 2003. Cell death in Pseudomonas aeruginosa biofilm development. J Bacteriol 185 : 45854592.[PubMed] [CrossRef]
175. Webb JS,, Givskov M,, Kjelleberg S . 2003. Bacterial biofilms: prokaryotic adventures in multicellularity. Curr Opin Microbiol 6 : 578585.[PubMed] [CrossRef]
176. Mikkelsen H,, Sivaneson M,, Filloux A . 2011. Key two-component regulatory systems that control biofilm formation in Pseudomonas aeruginosa . Environ Microbiol 13 : 16661681.[PubMed] [CrossRef]
177. Aguilar C,, Vlamakis H,, Losick R,, Kolter R . 2007. Thinking about Bacillus subtilis as a multicellular organism. Curr Opin Microbiol 10 : 638643.[PubMed] [CrossRef]
178. Klausen M,, Aaes-Jørgensen A,, Molin S,, Tolker-Nielsen T . 2003. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol Microbiol 50 : 6168.[PubMed] [CrossRef]
179. Klausen M,, Heydorn A,, Ragas P,, Lambertsen L,, Aaes-Jørgensen A,, Molin S,, Tolker-Nielsen T . 2003. Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol Microbiol 48 : 15111524.[PubMed] [CrossRef]
180. Boles BR,, Thoendel M,, Singh PK . 2005. Rhamnolipids mediate detachment of Pseudomonas aeruginosa from biofilms. Mol Microbiol 57 : 12101223.[PubMed] [CrossRef]
181. Pamp SJ,, Tolker-Nielsen T . 2007. Multiple roles of biosurfactants in structural biofilm development by Pseudomonas aeruginosa . J Bacteriol 189 : 25312539.[PubMed] [CrossRef]
182. Barken KB,, Pamp SJ,, Yang L,, Gjermansen M,, Bertrand JJ,, Klausen M,, Givskov M,, Whitchurch CB,, Engel JN,, Tolker-Nielsen T . 2008. Roles of type IV pili, flagellum-mediated motility and extracellular DNA in the formation of mature multicellular structures in Pseudomonas aeruginosa biofilms. Environ Microbiol 10 : 23312343.[PubMed] [CrossRef]
183. Yang L,, Nilsson M,, Gjermansen M,, Givskov M,, Tolker-Nielsen T . 2009. Pyoverdine and PQS mediated subpopulation interactions involved in Pseudomonas aeruginosa biofilm formation. Mol Microbiol 74 : 13801392.[PubMed] [CrossRef]
184. Harmsen M,, Yang L,, Pamp SJ,, Tolker-Nielsen T . 2010. An update on Pseudomonas aeruginosa biofilm formation, tolerance, and dispersal. FEMS Immunol Med Microbiol 59 : 253268.[PubMed] [CrossRef]
185. Haagensen JAJ,, Klausen M,, Ernst RK,, Miller SI,, Folkesson A,, Tolker-Nielsen T,, Molin S . 2007. Differentiation and distribution of colistin- and sodium dodecyl sulfate-tolerant cells in Pseudomonas aeruginosa biofilms. J Bacteriol 189 : 2837.[CrossRef]
186. Beatson SA,, Whitchurch CB,, Sargent JL,, Levesque RC,, Mattick JS . 2002. Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa . J Bacteriol 184 : 36053613.[PubMed] [CrossRef]
187. Tolker-Nielsen T,, Brinch UC,, Ragas PC,, Andersen JB,, Jacobsen CS,, Molin S . 2000. Development and dynamics of Pseudomonas sp. biofilms. J Bacteriol 182 : 64826489.[PubMed] [CrossRef]
188. Pamp SJ,, Gjermansen M,, Johansen HK,, Tolker-Nielsen T . 2008. Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol Microbiol 68 : 223240.[PubMed] [CrossRef]
189. Kievit TRD,, Gillis R,, Marx S,, Brown C,, Iglewski BH . 2001. Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Appl Environ Microbiol 67 : 18651873.[PubMed] [CrossRef]
190. Lequette Y,, Greenberg EP . 2005. Timing and localization of rhamnolipid synthesis gene expression in Pseudomonas aeruginosa biofilms. J Bacteriol 187 : 3744.[PubMed] [CrossRef]
191. Kaneko Y,, Thoendel M,, Olakanmi O,, Britigan BE,, Singh PK . 2007. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J Clin Invest 117 : 877888.[PubMed] [CrossRef]
192. Yang L,, Barken KB,, Skindersoe ME,, Christensen AB,, Givskov M,, Tolker-Nielsen T . 2007. Effects of iron on DNA release and biofilm development by Pseudomonas aeruginosa . Microbiology 153 : 13181328.[PubMed] [CrossRef]
193. Davies DG,, Parsek MR,, Pearson JP,, Iglewski BH,, Costerton JW,, Greenberg EP . 1998. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280 : 295298.[PubMed] [CrossRef]
194. Sauer K,, Camper AK,, Ehrlich GD,, Costerton JW,, Davies DG . 2002. Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 184 : 11401154.[PubMed] [CrossRef]
195. Heydorn A,, Ersbøll B,, Kato J,, Hentzer M,, Parsek MR,, Tolker-Nielsen T,, Givskov M,, Molin S . 2002. Statistical analysis of Pseudomonas aeruginosa biofilm development: impact of mutations in genes involved in twitching motility, cell-to-cell signaling, and stationary-phase sigma factor expression. Appl Environ Microbiol 68 : 20082017.[PubMed] [CrossRef]
196. Allesen-Holm M,, Barken KB,, Yang L,, Klausen M,, Webb JS,, Kjelleberg S,, Molin S,, Givskov M,, Tolker-Nielsen T . 2006. A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Mol Microbiol 59 : 11141128.[PubMed] [CrossRef]
197. Shrout JD,, Chopp DL,, Just CL,, Hentzer M,, Givskov M,, Parsek MR . 2006. The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional. Mol Microbiol 62 : 12641277.[PubMed] [CrossRef]
198. Ochsner UA,, Reiser J . 1995. Autoinducer-mediated regulation of rhamnolipid biosurfactant synthesis in Pseudomonas aeruginosa . Proc Natl Acad Sci USA 92 : 64246428.[CrossRef]
199. Davey ME,, Caiazza NC,, O’Toole GA . 2003. Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J Bacteriol 185 : 10271036.[PubMed] [CrossRef]
200. Purevdorj-Gage B,, Costerton WJ,, Stoodley P . 2005. Phenotypic differentiation and seeding dispersal in non-mucoid and mucoid Pseudomonas aeruginosa biofilms. Microbiology 151 : 15691576.[PubMed] [CrossRef]
201. Whitchurch CB,, Tolker-Nielsen T,, Ragas PC,, Mattick JS . 2002. Extracellular DNA required for bacterial biofilm formation. Science 295 : 1487. [PubMed] [CrossRef]
202. Matsukawa M,, Greenberg EP . 2004. Putative exopolysaccharide synthesis genes influence Pseudomonas aeruginosa biofilm development. J Bacteriol 186 : 44494456.[PubMed] [CrossRef]
203. D’Argenio DA,, Calfee MW,, Rainey PB,, Pesci EC . 2002. Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants. J Bacteriol 184 : 64816489.[PubMed] [CrossRef]
204. Bjarnsholt T,, Jensen ,, Burmølle M,, Hentzer M,, Haagensen JAJ,, Hougen HP,, Calum H,, Madsen KG,, Moser C,, Molin S,, Høiby N,, Givskov M . 2005. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151 : 373383.[PubMed] [CrossRef]
205. Banin E,, Brady KM,, Greenberg EP . 2006. Chelator-induced dispersal and killing of Pseudomonas aeruginosa cells in a biofilm. Appl Environ Microbiol 72 : 20642069.[PubMed] [CrossRef]
206. Banin E,, Vasil ML,, Greenberg EP . 2005. Iron and Pseudomonas aeruginosa biofilm formation. Proc Natl Acad Sci USA 102 : 1107611081.[PubMed] [CrossRef]
207. Klausen M,, Gjermansen M,, Kreft JU,, Tolker-Nielsen T . 2006. Dynamics of development and dispersal in sessile microbial communities: examples from Pseudomonas aeruginosa and Pseudomonas putida model biofilms. FEMS Microbiol Lett 261 : 111.[PubMed] [CrossRef]
208. McDougald D,, Rice SA,, Barraud N,, Steinberg PD,, Kjelleberg S . 2012. Should we stay or should we go: mechanisms and ecological consequences for biofilm dispersal. Nat Rev Microbiol 10 : 3950.[PubMed]
209. Morgan R,, Kohn S,, Hwang S-H,, Hassett DJ,, Sauer K . 2006. BdlA, a chemotaxis regulator essential for biofilm dispersion in Pseudomonas aeruginosa . J Bacteriol 188 : 73357343.[PubMed] [CrossRef]
210. Petrova OE,, Sauer K . 2012. Dispersion by Pseudomonas aeruginosa requires an unusual posttranslational modification of BdlA. Proc Natl Acad Sci USA 109 : 1669016695.[PubMed] [CrossRef]
211. Sauer K,, Cullen MC,, Rickard AH,, Zeef LA,, Davies DG,, Gilbert P . 2004. Characterization of nutrient-induced dispersion in Pseudomonas aeruginosa PAO1 biofilm. J Bacteriol 186 : 73127326.[PubMed] [CrossRef]
212. Wagner VE,, Bushnell D,, Passador L,, Brooks AI,, Iglewski BH . 2003. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J Bacteriol 185 : 20802095.[PubMed] [CrossRef]
213. Barraud N,, Hassett DJ,, Hwang S-H,, Rice SA,, Kjelleberg S,, Webb JS . 2006. Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa . J Bacteriol 188 : 73447353.[CrossRef]
214. An S,, Wu J,, Zhang LH . 2010. Modulation of Pseudomonas aeruginosa biofilm dispersal by a cyclic-di-GMP phosphodiesterase with a putative hypoxia-sensing domain. Appl Environ Microbiol 76 : 81608173.[PubMed] [CrossRef]