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Noise in a phosphorelay drives stochastic entry into sporulation in Bacillus subtilis
Author(s) -
Russell Jonathan R,
Cabeen Matthew T,
Wiggins Paul A,
Paulsson Johan,
Losick Richard
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201796988
Subject(s) - bacillus subtilis , biology , histidine kinase , microbiology and biotechnology , transcription factor , transcription (linguistics) , positive feedback , phosphorylation , response regulator , biophysics , biochemistry , genetics , histidine , bacteria , mutant , gene , enzyme , linguistics , philosophy , engineering , electrical engineering
Entry into sporulation in Bacillus subtilis is governed by a phosphorelay in which phosphoryl groups from a histidine kinase are successively transferred via relay proteins to the response regulator Spo0A. Spo0A~P, in turn, sets in motion events that lead to asymmetric division and activation of the cell‐specific transcription factor σ F , a hallmark for entry into sporulation. Here, we have used a microfluidics‐based platform to investigate the activation of Spo0A and σ F in individual cells held under constant, sporulation‐inducing conditions. The principal conclusions were that: (i) activation of σ F occurs with an approximately constant probability after adaptation to conditions of nutrient limitation; (ii) activation of σ F is tightly correlated with, and preceded by, Spo0A~P reaching a high threshold level; (iii) activation of Spo0A takes place abruptly just prior to asymmetric division; and (iv) the primary source of noise in the activation of Spo0A is the phosphorelay. We propose that cells exhibit a constant probability of attaining a high threshold level of Spo0A~P due to fluctuations in the flux of phosphoryl groups through the phosphorelay.