The Matrix Reloaded: Probing the Extracellular Matrix Synchronizes Bacterial Communities

Abstract

In response to chemical communication, bacterial cells often organize themselves into complex multicellular communities that carry out specialized tasks. These communities are frequently referred to as biofilms, which involve collective behavior of different cell types. Like cells of multicellular eukaryotes, the biofilm cells are surrounded by self-produced polymers that constitute the extracellular matrix (ECM), which binds them to each other and to the surface. In multicellular eukaryotes, it has been evident for decades that cell-ECM interactions control multiple cellular processes during development. While cells, both in biofilms and in multicellular eukaryotes, are surrounded by ECM and activate various genetic programs, until recently it has been unclear whether cell-ECM interactions are recruited in bacterial communicative behaviors. In this review, we will describe the examples reported thus far for ECM involvement in control of cell behavior throughout the different stages of biofilm formation. The studies presented in this review provide a newly emerging perspective of the bacterial ECM as an active player in regulation of biofilm development.

FIG 1

Signals from the ECM during biofilm development. (Bottom panel) Scheme of the different stages of biofilm development. (I) Attachment, monolayer formation, and aggregation. (II) 3D structure development and patterning. (III) Dispersal. (Top panel) (A) P. aeruginosa PAO1 deposits trails of high local concentrations of ECM (in green) that attract other cells and induce further ECM production (114, 128). (B) In B. subtilis, inhibition of the rotation of the flagella, e.g., by the viscous environment of the ECM, induces ECM production (150, 151). (C) TasA (brown), a structural amyloid in B. subtilis ECM, can be toxic to vegetatively growing B. subtilis cells (80). (D) During B. subtilis biofilm development, ECM induces emergence of different cell subpopulations: motile cells, ECM-producing cells, and sporulating cells (31). (E) In S. aureus PSMs, peptides (purple) can create structural amyloid fibers (85) but have a destabilizing effect on the biofilm in their monomeric form (176). (F) In C. crescentus biofilms, eDNA induces dispersal by inhibiting the reattachment of the mature stalked cell by binding to the exopolysaccharides of the holdfast (dark brown) (175).

FIG 2

ECM-cell signaling induces positive-feedback in ECM production. There are three ECM-derived signals that induce ECM production in B. subtilis biofilms as follows. (A) Disruption of flagellar rotation, which can occur in the viscous ECM environment, causing DegS-dependent phosphorylation of DegU and induction of the pgs operon, yielding γ-PGA production, and of bslA, which forms the biofilm hydrophobic coat (150, 151). (B) The KinD kinase senses high osmotic pressure and phosphorylates Spo0A. Phosphorylated Spo0A leads to the activation (low Spo0A∼P) or deactivation (high Spo0A∼P) of the epsA-O operon for production of exopolysaccharides and of the tapA-sipW-tasA operon, inducing TasA amyloid fiber production (163–165). (C) EpsA-specific binding to B. subtilis exopolysaccharides causes inhibition of EpsAB autophosphorylation and phosphorylation of EpsE, which may then lead to increased ECM production (148).