Pulcherrimin formation controls growth arrest of the Bacillus subtilis biofilm

Sofia Arnaouteli, Daniel Matoz Fernandez, Michael Porter, Margarita Kalamara, James Abbott, Cait E. MacPhee, Fordyce Davidson, Nicola Stanley-Wall (Lead / Corresponding author)

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Abstract

Biofilm formation by Bacillus subtilis is a communal process that culminates in the formation of architecturally complex multicellular communities. Here we reveal that the transition of the biofilm into a nonexpanding phase constitutes a distinct step in the process of biofilm development. Using genetic analysis we show that B. subtilis strains lacking the ability to synthesize pulcherriminic acid form biofilms that sustain the expansion phase, thereby linking pulcherriminic acid to growth arrest. However, production of pulcherriminic acid is not sufficient to block expansion of the biofilm. It needs to be secreted into the extracellular environment where it chelates Fe 3+ from the growth medium in a nonenzymatic reaction. Utilizing mathematical modeling and a series of experimental methodologies we show that when the level of freely available iron in the environment drops below a critical threshold, expansion of the biofilm stops. Bioinformatics analysis allows us to identify the genes required for pulcherriminic acid synthesis in other Firmicutes but the patchwork presence both within and across closely related species suggests loss of these genes through multiple independent recombination events. The seemingly counterintuitive self-restriction of growth led us to explore if there were any benefits associated with pulcherriminic acid production. We identified that pulcherriminic acid producers can prevent invasion by neighboring communities through the generation of an “iron-free” zone, thereby addressing the paradox of pulcherriminic acid production by B. subtilis.

Original languageEnglish
Pages (from-to)13553-13562
Number of pages10
JournalProceedings of the National Academy of Sciences
Volume116
Issue number27
Early online date19 Jun 2019
DOIs
Publication statusPublished - 2 Jul 2019

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Biofilms
Bacillus subtilis
Growth
Iron
pulcherriminic acid
Computational Biology
Genetic Recombination
Genes

Keywords

  • Bacillus subtilis
  • Biofilm
  • Growth arrest
  • Pulcherrimin

Cite this

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title = "Pulcherrimin formation controls growth arrest of the Bacillus subtilis biofilm",
abstract = "Biofilm formation by Bacillus subtilis is a communal process that culminates in the formation of architecturally complex multicellular communities. Here we reveal that the transition of the biofilm into a nonexpanding phase constitutes a distinct step in the process of biofilm development. Using genetic analysis we show that B. subtilis strains lacking the ability to synthesize pulcherriminic acid form biofilms that sustain the expansion phase, thereby linking pulcherriminic acid to growth arrest. However, production of pulcherriminic acid is not sufficient to block expansion of the biofilm. It needs to be secreted into the extracellular environment where it chelates Fe 3+ from the growth medium in a nonenzymatic reaction. Utilizing mathematical modeling and a series of experimental methodologies we show that when the level of freely available iron in the environment drops below a critical threshold, expansion of the biofilm stops. Bioinformatics analysis allows us to identify the genes required for pulcherriminic acid synthesis in other Firmicutes but the patchwork presence both within and across closely related species suggests loss of these genes through multiple independent recombination events. The seemingly counterintuitive self-restriction of growth led us to explore if there were any benefits associated with pulcherriminic acid production. We identified that pulcherriminic acid producers can prevent invasion by neighboring communities through the generation of an “iron-free” zone, thereby addressing the paradox of pulcherriminic acid production by B. subtilis.",
keywords = "Bacillus subtilis, Biofilm, Growth arrest, Pulcherrimin",
author = "Sofia Arnaouteli and {Matoz Fernandez}, Daniel and Michael Porter and Margarita Kalamara and James Abbott and MacPhee, {Cait E.} and Fordyce Davidson and Nicola Stanley-Wall",
note = "Work in the NSW, CEM, and FAD groups is supported by the Biotechnology and Biological Sciences Research Council [BB/P001335/1; BB/R012415/1]. MK is supported by a Biotechnology and Biological Sciences Research Council studentship [BB/M010996/1]. We would like to acknowledge the Dundee Imaging Facility, Dundee, which is supported by the 'Wellcome Trust Technology Platform' award [097945/B/11/Z] and the 'MRC Next Generation Optical Microscopy' award [MR/K015869/1].",
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T1 - Pulcherrimin formation controls growth arrest of the Bacillus subtilis biofilm

AU - Arnaouteli, Sofia

AU - Matoz Fernandez, Daniel

AU - Porter, Michael

AU - Kalamara, Margarita

AU - Abbott, James

AU - MacPhee, Cait E.

AU - Davidson, Fordyce

AU - Stanley-Wall, Nicola

N1 - Work in the NSW, CEM, and FAD groups is supported by the Biotechnology and Biological Sciences Research Council [BB/P001335/1; BB/R012415/1]. MK is supported by a Biotechnology and Biological Sciences Research Council studentship [BB/M010996/1]. We would like to acknowledge the Dundee Imaging Facility, Dundee, which is supported by the 'Wellcome Trust Technology Platform' award [097945/B/11/Z] and the 'MRC Next Generation Optical Microscopy' award [MR/K015869/1].

PY - 2019/7/2

Y1 - 2019/7/2

N2 - Biofilm formation by Bacillus subtilis is a communal process that culminates in the formation of architecturally complex multicellular communities. Here we reveal that the transition of the biofilm into a nonexpanding phase constitutes a distinct step in the process of biofilm development. Using genetic analysis we show that B. subtilis strains lacking the ability to synthesize pulcherriminic acid form biofilms that sustain the expansion phase, thereby linking pulcherriminic acid to growth arrest. However, production of pulcherriminic acid is not sufficient to block expansion of the biofilm. It needs to be secreted into the extracellular environment where it chelates Fe 3+ from the growth medium in a nonenzymatic reaction. Utilizing mathematical modeling and a series of experimental methodologies we show that when the level of freely available iron in the environment drops below a critical threshold, expansion of the biofilm stops. Bioinformatics analysis allows us to identify the genes required for pulcherriminic acid synthesis in other Firmicutes but the patchwork presence both within and across closely related species suggests loss of these genes through multiple independent recombination events. The seemingly counterintuitive self-restriction of growth led us to explore if there were any benefits associated with pulcherriminic acid production. We identified that pulcherriminic acid producers can prevent invasion by neighboring communities through the generation of an “iron-free” zone, thereby addressing the paradox of pulcherriminic acid production by B. subtilis.

AB - Biofilm formation by Bacillus subtilis is a communal process that culminates in the formation of architecturally complex multicellular communities. Here we reveal that the transition of the biofilm into a nonexpanding phase constitutes a distinct step in the process of biofilm development. Using genetic analysis we show that B. subtilis strains lacking the ability to synthesize pulcherriminic acid form biofilms that sustain the expansion phase, thereby linking pulcherriminic acid to growth arrest. However, production of pulcherriminic acid is not sufficient to block expansion of the biofilm. It needs to be secreted into the extracellular environment where it chelates Fe 3+ from the growth medium in a nonenzymatic reaction. Utilizing mathematical modeling and a series of experimental methodologies we show that when the level of freely available iron in the environment drops below a critical threshold, expansion of the biofilm stops. Bioinformatics analysis allows us to identify the genes required for pulcherriminic acid synthesis in other Firmicutes but the patchwork presence both within and across closely related species suggests loss of these genes through multiple independent recombination events. The seemingly counterintuitive self-restriction of growth led us to explore if there were any benefits associated with pulcherriminic acid production. We identified that pulcherriminic acid producers can prevent invasion by neighboring communities through the generation of an “iron-free” zone, thereby addressing the paradox of pulcherriminic acid production by B. subtilis.

KW - Bacillus subtilis

KW - Biofilm

KW - Growth arrest

KW - Pulcherrimin

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U2 - 10.1073/pnas.1903982116

DO - 10.1073/pnas.1903982116

M3 - Article

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VL - 116

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EP - 13562

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

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