title: Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E.
abstract: Salmonella enterica serovar Typhi (S. typhi) causes typhoid fever. We show that exposure of S. typhi to neuroendocrine stress hormones results in haemolysis, which is associated with the release of haemolysin E in membrane vesicles. This effect is attributed to increased expression of the small RNA micA and RNA chaperone Hfq, with concomitant downregulation of outer membrane protein A. Deletion of micA or the two-component signal-transduction system, CpxAR, abolishes the phenotype. The hormone response is inhibited by the β-blocker propranolol. We provide mechanistic insights into the basis of neuroendocrine hormone-mediated haemolysis by S. typhi, increasing our understanding of inter-kingdom signalling.
authors.affiliation: Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle NE2 4HH, UK.
authors.forename: Michail H
authors.initials: MH
authors.lastname: Karavolos
authors.forename: David M
authors.initials: DM
authors.lastname: Bulmer
authors.forename: Hannah
authors.initials: H
authors.lastname: Spencer
authors.forename: Giordano
authors.initials: G
authors.lastname: Rampioni
authors.forename: Ira
authors.initials: I
authors.lastname: Schmalen
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.forename: Joe
authors.initials: J
authors.lastname: Gray
authors.forename: Maria
authors.initials: M
authors.lastname: Fookes
authors.forename: Klaus
authors.initials: K
authors.lastname: Winzer
authors.forename: Alasdair
authors.initials: A
authors.lastname: Ivens
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.forename: C M Anjam
authors.initials: CM
authors.lastname: Khan
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004837:Epinephrine / Q000494:pharmacology / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D006461:Hemolysis; D006728:Hormones / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011433:Propranolol / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012485:Salmonella typhi / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D006728:Hormones; C078167:OMPA outer membrane proteins; D011433:Propranolol; D011494:Protein Kinases; C092472:CpxA protein, bacteria; D009638:Norepinephrine; D004837:Epinephrine