Editors' ChoiceMicrobiology

Biofilm Positive Feedback

Sci. Signal.  12 Aug 2014:
Vol. 7, Issue 338, pp. ec215
DOI: 10.1126/scisignal.2005779

Many species of bacteria can exist as free-living, motile cells or as biofilms in which nonmotile cells are bound together by a secreted extracellular matrix that includes exopolysaccharide (EPS). In the Gram-positive bacterium Bacillus subtilis, the operon containing genes required for EPS production (EpsA-O) is repressed in motile cells and derepressed as cells form biofilms. Elsholz et al. report that two proteins encoded by genes in this operon, EpsA and EpsB, together form a two-component tyrosine kinase (EpsAB) that is sensitive to EPS and mediates posttranslational positive feedback of EPS production. Based on similarity to other conserved bacterial two-component kinases, EpsA was predicted to be an integral membrane protein, and EpsB was predicted to be a cytoplasmic tyrosine kinase. EpsA and EpsB were required for maximal production of EPS. In the absence of EPS, EpsB underwent inactivating autophosphorylation, and EPS dose-dependently blocked EpsB autophosphorylation. During biofilm formation, when EPS production increases, EpsB phosphorylated the glycosyltransferase EpsE, which is required for EPS biosynthesis, suggesting that phosphorylation activates this enzyme. In early stages of biofilm formation, EpsB was unphosphorylated and EpsE was phosphorylated. In late stages of biofilm maturation, the abundance of unphosphorylated EpsE decreased and EpsB became autophosphorylated. The authors propose that the basal amounts of EPS produced by motile cells could trigger an increase in EPS production in nearby cells to promote biofilm formation. These findings indicate that EPS can act as an extracellular signal similar to secreted quorum signals. In bacterial quorum-sensing systems, accumulation of a secreted molecule in high-density populations triggers a coordinated transcriptional response across the population. Genes that generate the signal itself are among those stimulated when a quorum has been reached, creating a positive feedback loop that reinforces the coordinated group response. Whereas positive feedback in these quorum-sensing pathways is mediated by transcriptional regulation, the EPS-EpsAB system stimulates biosynthesis of the signal through changes in posttranslational modifications.

A. K. W. Elsholz, S. A. Wacker, R. Losick, Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase. Genes Dev. 28, 1710–1720 (2014). [PubMed]