Concerted Actions of a Thermo-labile Regulator and a Unique Intergenic RNA Thermosensor Control Yersinia Virulence

PLoS Pathogens

Rebekka Steinmann¹  Franz Narberhaus¹  Hans Wolf-Watz¹  Jens Kortmann¹  Evelin Berger¹  Fabio Pisano¹  Stephanie Seekircher²  Petra Dersch²  Tanja Thiermann³  Katja Böhme³  Ann Kathrin Heroven⁴ 

[1] Abteilung Molekulare Infektionsbiologie, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany;Department of Molecular Biology, Laboratory of Molecular Infectious Medicine, Umeå University, Umeå, Sweden;Institut für Mikrobiologie, Technische Universität Braunschweig, Braunschweig, Germany;Lehrstuhl für Biologie der Mikroorganismen, Ruhr-Universität Bochum, Bochum, Germany

关键词: Yersinia pseudotuberculosis;    Thermometers;    Polymerase chain reaction;    Yersinia;    Body temperature;    RNA structure;    Virulence factors;    Mutant strains;   

DOI  :  10.1371/journal.ppat.1002518

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY