RT Journal Article
SR Electronic
T1 Ribosome provisioning activates a bistable switch coupled to fast exit from stationary phase
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 244129
DO 10.1101/244129
A1 P. Remigi
A1 G.C. Ferguson
A1 S. De Monte
A1 P.B. Rainey
YR 2018
UL http://biorxiv.org/content/early/2018/04/24/244129.abstract
AB Observations of bacteria at the single-cell level have revealed many instances of phenotypic heterogeneity within otherwise clonal populations, but the selective causes, molecular bases and broader ecological relevance remain poorly understood. In an earlier experiment in which the bacterium Pseudomonas fluorescens SBW25 was propagated under a selective regime that mimicked the host immune response, a genotype evolved that stochastically switched between capsulation states. The genetic cause was a mutation in carB that decreased the pyrimidine pool (and growth rate), lowering the activation threshold of a pre-existing but hitherto unrecognised phenotypic switch. Genetic components surrounding bifurcation of UTP flux towards DNA/RNA or UDP-glucose (a precursor of colanic acid forming the capsules) were implicated as key components. Extending these molecular analyses – and based on a combination of genetics, transcriptomics, biochemistry and mathematical modelling – we show that pyrimidine limitation triggers an increase in ribosome biosynthesis and that switching is caused by competition between ribosomes and CsrA/RsmA proteins for the mRNA transcript of a feed-forward regulator of colanic acid biosynthesis. We additionally show that in the ancestral bacterium the switch is part of a programme that determines stochastic entry into the semi-quiescent capsulated state, ensures that such cells are provisioned with excess ribosomes, and enables provisioned cells to exit rapidly from stationary phase under permissive conditions.