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Medientyp:
E-Artikel
Titel:
RNA target profiles direct the discovery of virulence functions for the cold-shock proteins CspC and CspE
Beteiligte:
Michaux, Charlotte;
Holmqvist, Erik;
Vasicek, Erin;
Sharan, Malvika;
Barquist, Lars;
Westermann, Alexander J.;
Gunn, John S.;
Vogel, Jörg
Erschienen:
National Academy of Sciences, 2017
Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
ISSN:
1091-6490;
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>The functions of many bacterial RNA-binding proteins remain obscure because of a lack of knowledge of their cellular ligands. Although well-studied cold-shock protein A (CspA) family members are induced and function at low temperature, others are highly expressed in infection-relevant conditions. Here, we have profiled transcripts bound in vivo by the CspA family members of <italic>Salmonella enterica</italic> serovar Typhimurium to link the constitutively expressed CspC and CspE proteins with virulence pathways. Phenotypic assays in vitro demonstrated a crucial role for these proteins in membrane stress, motility, and biofilm formation. Moreover, double deletion of <italic>cspC</italic> and <italic>cspE</italic> fully attenuates <italic>Salmonella</italic> in systemic mouse infection. In other words, the RNA ligand-centric approach taken here overcomes a problematic molecular redundancy of CspC and CspE that likely explains why these proteins have evaded selection in previous virulence factor screens in animals. Our results highlight RNA-binding proteins as regulators of pathogenicity and potential targets of antimicrobial therapy. They also suggest that globally acting RNA-binding proteins are more common in bacteria than currently appreciated.</p>