title: ComGA-RelA interaction and persistence in the Bacillus subtilis K-state.
abstract: The bistably expressed K-state of Bacillus subtilis is characterized by two distinct features; transformability and arrested growth when K-state cells are exposed to fresh medium. The arrest is manifested by a failure to assemble replisomes and by decreased rates of cell growth and rRNA synthesis. These phenotypes are all partially explained by the presence of the AAA(+) protein ComGA, which is also required for the binding of transforming DNA to the cell surface and for the assembly of the transformation pilus that mediates DNA transport. We have discovered that ComGA interacts with RelA and that the ComGA-dependent inhibition of rRNA synthesis is largely bypassed in strains that cannot synthesize the alarmone (p)ppGpp. We propose that the interaction of ComGA with RelA prevents the hydrolysis of (p)ppGpp in K-state cells, which are thus trapped in a non-growing state until ComGA is degraded. We show that some K-state cells exhibit tolerance to antibiotics, a form of type 1 persistence, and we propose that the bistable expression of both transformability and the growth arrest are bet-hedging adaptations that improve fitness in the face of varying environments, such as those presumably encountered by B. subtilis in the soil.
authors.affiliation: Public Health Research Institute Center of New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ, 07103, USA.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Public Health Research Institute Center of New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ, 07103, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Tanner
authors.affiliation: Public Health Research Institute Center of New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ, 07103, USA.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Carabetta
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
authors.forename: Ileana M
authors.initials: IM
authors.lastname: Cristea
authors.affiliation: Public Health Research Institute Center of New Jersey Medical School, Rutgers University, 225 Warren Street, Newark, NJ, 07103, USA.
authors.forename: David
authors.initials: D
authors.lastname: Dubnau
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000254:growth & development*; D001426:Bacterial Proteins / Q000378:metabolism*; D002455:Cell Division; D061269:DNA Transformation Competence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006158:Guanosine Pentaphosphate / Q000378:metabolism; D006159:Guanosine Tetraphosphate / Q000378:metabolism; D008025:Ligases / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012335:RNA, Ribosomal / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; C061262:ComA protein, Bacteria; D004268:DNA-Binding Proteins; D012335:RNA, Ribosomal; D006159:Guanosine Tetraphosphate; D006158:Guanosine Pentaphosphate; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases