title: ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes.
abstract: For a new pathogen to emerge, it must acquire both virulence genes and a system for responding to changes in environmental conditions. Starvation of nutrients or growth arrest induces the stringent response in Escherichia coli, via increased ppGpp. We found the adherence capacity of enterohaemorrhagic E. coli (EHEC) and gene expression in the locus of enterocyte effacement (LEE) were enhanced by a downshift in nutrients or by entry into the stationary growth phase, both of which increase the ppGpp concentration. The activation was dependent on relA and spoT, which encode enzymes for the synthesis and degradation of ppGpp, and on dksA, which encodes an RNA polymerase accessory protein required for the stringent response. Upon induction of RelA expression, LEE gene transcription was activated within 20 min, even without starvation. The expression of two LEE transcriptional regulators, Ler and Pch, was activated by ppGpp and essential for the enhancement of LEE gene expression. In addition, the ler and pch promoters were directly activated by ppGpp in an in vitro transcription system. These findings suggest that the regulation of virulence genes in EHEC is integrated with E. coli's stringent response system, through the regulation of virulence regulatory genes.
authors.affiliation: Division of Applied Microbiology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Ogura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tashiro
authors.forename: Satoru
authors.initials: S
authors.lastname: Kuhara
authors.forename: Nakaba
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Toru
authors.initials: T
authors.lastname: Tobe
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D004927:Escherichia coli Infections / Q000382:microbiology; D019453:Escherichia coli O157 / Q000235:genetics* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D044404:Genomic Islands / Q000235:genetics*; D006159:Guanosine Tetraphosphate / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; C457340:LEE protein, E coli; D010750:Phosphoproteins; D051996:Transcription Factor RelA; D014157:Transcription Factors; C090751:dksA protein, E coli; D006159:Guanosine Tetraphosphate