title: Virulence in Pectobacterium atrosepticum is regulated by a coincidence circuit involving quorum sensing and the stress alarmone, (p)ppGpp.
abstract: Pectobacterium atrosepticum (Pca) is a Gram-negative phytopathogen which causes disease by secreting plant cell wall degrading exoenzymes (PCWDEs). Previous studies have shown that PCWDE production is regulated by (i) the intercellular quorum sensing (QS) signal molecule, 3-oxo-hexanoyl-l-homoserine lactone (OHHL), and (ii) the intracellular 'alarmone', (p)ppGpp, which reports on nutrient limitation. Here we show that these two signals form an integrated coincidence circuit which ensures that metabolically costly PCWDE synthesis does not occur unless the population is simultaneously quorate and nutrient limited. A (p)ppGpp null ΔrelAΔspoT mutant was defective in both OHHL and PCWDE production, and nutritional supplementation of wild type cultures (which suppresses (p)ppGpp production) also suppressed OHHL and PCWDE production. There was a substantial overlap in the transcriptome of a (p)ppGpp deficient relA mutant and of a QS defective expI (OHHL synthase) mutant, especially with regards to virulence-associated genes. Random transposon mutagenesis revealed that disruption of rsmA was sufficient to restore PCWDE production in the (p)ppGpp null strain. We found that the ratio of RsmA protein to its RNA antagonist, rsmB, was modulated independently by (p)ppGpp and QS. While QS predominantly controlled virulence by modulating RsmA levels, (p)ppGpp exerted regulation through the modulation of the RsmA antagonist, rsmB.
authors: Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge, CB2 1QW, UK.
authors: Steven D
authors: SD
authors: Bowden
authors: Alison
authors: A
authors: Eyres
authors: Jade C S
authors: JC
authors: Chung
authors: Rita E
authors: RE
authors: Monson
authors: Arthur
authors: A
authors: Thompson
authors: George P C
authors: GP
authors: Salmond
authors: David R
authors: DR
authors: Spring
authors: Martin
authors: M
authors: Welch
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D006159:Guanosine Tetraphosphate / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D044043:Pectobacterium / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D053038:Quorum Sensing; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C088386:homoserine lactone; D006159:Guanosine Tetraphosphate; D015107:4-Butyrolactone