Master regulators of phenotypic differentiation in B.
subtilis
In B. subtilis , the response regulators DegU, Spo0A, and ComA are
recognized as the master switches that control the development of
population heterogeneity . The activity of these three heterogeneity
modulators depends on the ratios of the respective proteins in their
non-phosphorylated and phosphorylated states (phosphorylated regulators
are henceforth indicated with ∼P). In general, the phosphorylation state
affects the regulator’s affinity for the promotor regions of the genes
that they regulate . Delicate modulation of these ratios allows B.
subtilis to develop a heterogeneous population, where cells adapt to
small environmental differences (micro-niches) within the population,
especially in the spatial structure of biofilms .
DegU is the response regulator of the DegS/U two component system. DegS
is a cytoplasmic sensor histidine kinase that directly phosphorylates
DegU. The DegU regulon is extensive and includes genes associated to
motility (e.g. flagellum production) and biofilm formation (e.g.
hydrophobin protein and exoenzymes needed for substrate degradation) .
Non-phosphorylated DegU activates competence development, while
depending on the relative amount of DegU∼P different sets of genes of
its regulon are transcribed that provide a smooth transition from
surface spreading to settlement during biofilm development .
Spo0A is a transcriptional regulator that controls the expression of
hundreds of genes and operons in B. subtilis important among
others for biofilm matrix production and the generation of spores .
Spo0A is phosphorylated via a phosphorelay that can be initiated by any
of five known independent histidine kinases (KinA, KinB, KinC, KinD, and
KinE) . Once activated by their cognate signals, the Kin kinases
phosphorylate the response regulator Spo0F, which in turn transfers the
phosphoryl group to a secondary response regulator, Spo0B, which finally
phosphorylates Spo0A. Like DegU, the amount of Spo0A∼P in the cells
determines which of its target genes are expressed .
The third major master switch of population heterogeneity in B.
subtilis , ComA, is directly modulated by a quorum sensing (QS) system .
QS is a common cell-communication strategy that relies on the production
and detection of extracellular autoinducer signaling molecules by cells
of the same species . ComA-related QS system uses the ComX peptide as
its autoinducer and the membrane localized ComP histidine kinase as
sensor. The extracellular ComX signal activates ComP, leading to
autophosphorylation and transfer of phosphate to ComA . Once
phosphorylated, ComA controls the production of surfactin (an important
surfactant lipopeptide), and the development of competence in B.
subtilis cells .