Concerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence.

2.50
HDL Handle:
http://hdl.handle.net/10033/228372
Title:
Concerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence.
Authors:
Böhme, Katja; Steinmann, Rebekka; Kortmann, Jens; Seekircher, Stephanie; Heroven, Ann Kathrin; Berger, Evelin; Pisano, Fabio; Thiermann, Tanja; Wolf-Watz, Hans; Narberhaus, Franz; Dersch, Petra
Abstract:
Expression of all Yersinia pathogenicity factors encoded on the virulence plasmid, including the yop effector and the ysc type III secretion genes, is controlled by the transcriptional activator LcrF in response to temperature. Here, we show that a protein- and RNA-dependent hierarchy of thermosensors induce LcrF synthesis at body temperature. Thermally regulated transcription of lcrF is modest and mediated by the thermo-sensitive modulator YmoA, which represses transcription from a single promoter located far upstream of the yscW-lcrF operon at moderate temperatures. The transcriptional response is complemented by a second layer of temperature-control induced by a unique cis-acting RNA element located within the intergenic region of the yscW-lcrF transcript. Structure probing demonstrated that this region forms a secondary structure composed of two stemloops at 25°C. The second hairpin sequesters the lcrF ribosomal binding site by a stretch of four uracils. Opening of this structure was favored at 37°C and permitted ribosome binding at host body temperature. Our study further provides experimental evidence for the biological relevance of an RNA thermometer in an animal model. Following oral infections in mice, we found that two different Y. pseudotuberculosis patient isolates expressing a stabilized thermometer variant were strongly reduced in their ability to disseminate into the Peyer's patches, liver and spleen and have fully lost their lethality. Intriguingly, Yersinia strains with a destabilized version of the thermosensor were attenuated or exhibited a similar, but not a higher mortality. This illustrates that the RNA thermometer is the decisive control element providing just the appropriate amounts of LcrF protein for optimal infection efficiency.
Affiliation:
Institut für Mikrobiologie, Technische Universität Braunschweig, Braunschweig, Germany.
Citation:
Concerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence. 2012, 8 (2):e1002518 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Feb-2012
URI:
http://hdl.handle.net/10033/228372
DOI:
10.1371/journal.ppat.1002518
PubMed ID:
22359501
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
Publications of Molekulare Infektionsbiologie(MIBI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorBöhme, Katjaen_GB
dc.contributor.authorSteinmann, Rebekkaen_GB
dc.contributor.authorKortmann, Jensen_GB
dc.contributor.authorSeekircher, Stephanieen_GB
dc.contributor.authorHeroven, Ann Kathrinen_GB
dc.contributor.authorBerger, Evelinen_GB
dc.contributor.authorPisano, Fabioen_GB
dc.contributor.authorThiermann, Tanjaen_GB
dc.contributor.authorWolf-Watz, Hansen_GB
dc.contributor.authorNarberhaus, Franzen_GB
dc.contributor.authorDersch, Petraen_GB
dc.date.accessioned2012-06-11T14:01:33Z-
dc.date.available2012-06-11T14:01:33Z-
dc.date.issued2012-02-
dc.identifier.citationConcerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence. 2012, 8 (2):e1002518 PLoS Pathog.en_GB
dc.identifier.issn1553-7374-
dc.identifier.pmid22359501-
dc.identifier.doi10.1371/journal.ppat.1002518-
dc.identifier.urihttp://hdl.handle.net/10033/228372-
dc.description.abstractExpression of all Yersinia pathogenicity factors encoded on the virulence plasmid, including the yop effector and the ysc type III secretion genes, is controlled by the transcriptional activator LcrF in response to temperature. Here, we show that a protein- and RNA-dependent hierarchy of thermosensors induce LcrF synthesis at body temperature. Thermally regulated transcription of lcrF is modest and mediated by the thermo-sensitive modulator YmoA, which represses transcription from a single promoter located far upstream of the yscW-lcrF operon at moderate temperatures. The transcriptional response is complemented by a second layer of temperature-control induced by a unique cis-acting RNA element located within the intergenic region of the yscW-lcrF transcript. Structure probing demonstrated that this region forms a secondary structure composed of two stemloops at 25°C. The second hairpin sequesters the lcrF ribosomal binding site by a stretch of four uracils. Opening of this structure was favored at 37°C and permitted ribosome binding at host body temperature. Our study further provides experimental evidence for the biological relevance of an RNA thermometer in an animal model. Following oral infections in mice, we found that two different Y. pseudotuberculosis patient isolates expressing a stabilized thermometer variant were strongly reduced in their ability to disseminate into the Peyer's patches, liver and spleen and have fully lost their lethality. Intriguingly, Yersinia strains with a destabilized version of the thermosensor were attenuated or exhibited a similar, but not a higher mortality. This illustrates that the RNA thermometer is the decisive control element providing just the appropriate amounts of LcrF protein for optimal infection efficiency.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen_GB
dc.titleConcerted actions of a thermo-labile regulator and a unique intergenic RNA thermosensor control Yersinia virulence.en
dc.typeArticleen
dc.contributor.departmentInstitut für Mikrobiologie, Technische Universität Braunschweig, Braunschweig, Germany.en_GB
dc.identifier.journalPLoS pathogensen_GB
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