title: Hfq negatively regulates type III secretion in EHEC and several other pathogens.
abstract: Hfq is a conserved RNA-binding protein that regulates diverse cellular processes through post-transcriptional control of gene expression, often by functioning as a chaperone for regulatory sRNAs. Here, we explored the role of Hfq in enterohaemorrhagic Escherichia coli (EHEC), a group of non-invasive intestinal pathogens. EHEC virulence is dependent on a Type III secretion system encoded in the LEE pathogenicity island. The abundance of transcripts for all 41 LEE genes and more than half of confirmed non-LEE-encoded T3 effectors were elevated in an EHEC hfq deletion mutant. Thus, Hfq promotes co-ordinated expression of the LEE-encoded T3S apparatus and both LEE- and non-LEE-encoded effectors. Increased transcript levels led to the formation of functional secretion complexes capable of secreting high quantities of effectors into the supernatant. The increase in LEE-derived transcripts and proteins was dependent on Ler, the LEE-encoded transcriptional activator, and the ler transcript appears to be a direct target of Hfq-mediated negative regulation. Finally, we found that Hfq contributes to the negative regulation of T3SSs in several other pathogens, suggesting that Hfq, potentially along with species-specific sRNAs, underlies a common means to prevent unfettered expression of T3SSs.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Shakhnovich
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D054324:Enterohemorrhagic Escherichia coli / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D035001:Host Factor 1 Protein / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D013489:Suppression, Genetic; D015534:Trans-Activators / Q000378:metabolism; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins; C087373:Hfq protein, E coli; D035001:Host Factor 1 Protein; C465556:Ler protein, E coli; D012329:RNA, Bacterial; D012333:RNA, Messenger; D015534:Trans-Activators
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