title: Transient heterogeneity in extracellular protease production by Bacillus subtilis.
abstract: The most sophisticated survival strategy Bacillus subtilis employs is the differentiation of a subpopulation of cells into highly resistant endospores. To examine the expression patterns of non-sporulating cells within heterogeneous populations, we used buoyant density centrifugation to separate vegetative cells from endospore-containing cells and compared the transcriptome profiles of both subpopulations. This demonstrated the differential expression of various regulons. Subsequent single-cell analyses using promoter-gfp fusions confirmed our microarray results. Surprisingly, only part of the vegetative subpopulation highly and transiently expresses genes encoding the extracellular proteases Bpr (bacillopeptidase) and AprE (subtilisin), both of which are under the control of the DegU transcriptional regulator. As these proteases and their degradation products freely diffuse within the liquid growth medium, all cells within the clonal population are expected to benefit from their activities, suggesting that B. subtilis employs cooperative or even altruistic behavior. To unravel the mechanisms by which protease production heterogeneity within the non-sporulating subpopulation is established, we performed a series of genetic experiments combined with mathematical modeling. Simulations with our model yield valuable insights into how population heterogeneity may arise by the relatively long and variable response times within the DegU autoactivating pathway.
authors.affiliation: Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Haren, The Netherlands.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Veening
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Igoshin
authors.forename: Robyn T
authors.initials: RT
authors.lastname: Eijlander
authors.forename: Reindert
authors.initials: R
authors.lastname: Nijland
authors.forename: Leendert W
authors.initials: LW
authors.lastname: Hamoen
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
mesh_terms: D001412:Bacillus subtilis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D003198:Computer Simulation; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins / Q000378:metabolism; D008954:Models, Biological; D015233:Models, Statistical; D008962:Models, Theoretical; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010447:Peptide Hydrolases / Q000378:metabolism*; D013171:Spores, Bacterial / Q000378:metabolism; D049490:Systems Biology; D014158:Transcription, Genetic
chemical_list: C088074:AprE protein, Bacteria; D001426:Bacterial Proteins; C066497:DegU protein, Bacteria; D026901:Membrane Transport Proteins; D010447:Peptide Hydrolases