title: A plasmid-borne Rap-Phr system of Bacillus subtilis can mediate cell-density controlled production of extracellular proteases.
abstract: Bacillus subtilis uses two-component signal transduction systems to sense intra- and extracellular stimuli to adapt to fluctuating environmental situations. Regulator aspartate phosphatases (Raps) have important roles in these processes, as they can dephosphorylate certain response-regulators, and are themselves subject to cell-density-controlled inhibition by secreted Phr (phosphate regulator) peptides. Eleven chromosomal genes encode this family of phosphatases, but in addition, certain strains contain endogenous plasmids with genes for homologous Rap-Phr systems. Plasmid pTA1060 encodes Rap60 and its antagonistic signalling molecule Phr60. Strikingly, expression of Rap60 in B. subtilis 168 strongly repressed the production of proteolytic enzymes. In fact, the transcription of the aprE gene, encoding a major extracellular protease, was shown to be decreased upon Rap60 expression, whereas this effect could be antagonized by the extracellular addition of synthetic Phr60 pentapeptide. Finally, transcription studies suggest that Rap60 dephosphorylates a component of the phosphorelay and is coupled to aprE transcription by the transition-state regulator AbrB. In conclusion, these data show that endogenous plasmids contain functional Rap-Phr systems and for the first time, that Rap-Phr systems can mediate cell-density controlled production of secreted proteases. This quorum-sensing mechanism might enable B. subtilis to suppress protease production under conditions of low cell densities when nutrients are still available in sufficient amounts.
authors.affiliation: Department of Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, Kerklaan 30, 9751 NN Haren, The Netherlands.
authors.forename: Emmo J
authors.initials: EJ
authors.lastname: Koetje
authors.forename: Amra
authors.initials: A
authors.lastname: Hajdo-Milasinovic
authors.forename: Rense
authors.initials: R
authors.lastname: Kiewiet
authors.forename: Sierd
authors.initials: S
authors.lastname: Bron
authors.forename: Harold
authors.initials: H
authors.lastname: Tjalsma
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D026901:Membrane Transport Proteins; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids; D015398:Signal Transduction; D013171:Spores, Bacterial / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: C088074:AprE protein, Bacteria; D001426:Bacterial Proteins; D003470:Culture Media; D026901:Membrane Transport Proteins; D010455:Peptides; C445331:aspartyl phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D010450:Endopeptidases