title: Two small ncRNAs jointly govern virulence and transmission in Legionella pneumophila.
abstract: To transit from intra- to extracellular environments, Legionella pneumophila differentiates from a replicative/non-virulent to a transmissive/virulent form using the two-component system LetA/LetS and the global repressor protein CsrA. While investigating how both regulators act co-ordinately we characterized two ncRNAs, RsmY and RsmZ, that link the LetA/LetS and CsrA regulatory networks. We demonstrate that LetA directly regulates their expression and show that RsmY and RsmZ are functional in Escherichia coli and are able to bind CsrA in vitro. Single mutants have no (ΔrsmY) or a little (ΔrsmZ) impact on virulence, but the ΔrsmYZ strain shows a drastic defect in intracellular growth in Acanthamoeba castellanii and THP-1 monocyte-derived macrophages. Analysis of the transcriptional programmes of the ΔletA, ΔletS and ΔrsmYZ strains revealed that the switch to the transmissive phase is partially blocked. One major difference between the ΔletA, ΔletS and ΔrsmYZ strains was that the latter synthesizes flagella. Taken together, LetA activates transcription of RsmY and RsmZ, which sequester CsrA and abolish its post-transcriptional repressive activity. However, the RsmYZ-CsrA pathway appears not to be the main or only regulatory circuit governing flagella synthesis. We suggest that rather RpoS and LetA, by influencing LetE and probably cyclic-di-GMP levels, regulate motility in L. pneumophila.
authors.affiliation: Institut Pasteur, Biologie des Bactéries Intracellulaires and CNRS URA 2171, 28 Rue du Dr Roux, Paris, France.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sahr
authors.forename: Holger
authors.initials: H
authors.lastname: Brüggemann
authors.forename: Matthieu
authors.initials: M
authors.lastname: Jules
authors.forename: Mariella
authors.initials: M
authors.lastname: Lomma
authors.forename: Christiane
authors.initials: C
authors.lastname: Albert-Weissenberger
authors.forename: Christel
authors.initials: C
authors.lastname: Cazalet
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D022661:RNA, Untranslated