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)

Research output: Contribution to journalArticle

1 Citation (Scopus)
86 Downloads (Pure)

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

    Fingerprint

Keywords

  • Bacillus subtilis
  • Biofilm
  • Growth arrest
  • Pulcherrimin

Cite this