title: LeuO enhances butyrate-induced virulence expression through a positive regulatory loop in enterohaemorrhagic Escherichia coli.
abstract: Enterohaemorrhagic Escherichia coli (EHEC) causes bloody diarrhoea and other severe symptoms such as haemorrhagic uraemic syndrome. The expression of virulence genes on the locus for enterocyte effacement (LEE) and associated genes is regulated by a variety of factors, including transcriptional regulators and environmental signals. Butyrate, one of the major short-chain fatty acids present in the intestine, enhances expression of LEE genes and flagella biosynthesis genes in EHEC O157:H7, resulting in increased bacterial adherence and motility. Here, we show that expression of the leuO gene, which encodes a LysR-type transcriptional regulator, is enhanced by butyrate via Lrp, which is also necessary for butyrate-induced responses of LEE genes. LeuO expression induces prolonged activation of the promoter of LEE1 operon, including the ler gene, as well as virulence mechanisms such as microcolony formation. Activation of the LEE1 promoter by LeuO depends on another regulator, called Pch. The response of the leuO promoter to butyrate requires two virulence regulators, Pch and Ler, in addition to Lrp. Pch, Ler and Lrp bind the upstream region of the leuO promoter. Thus, leuO is involved in butyrate-enhanced expression of LEE genes through a positive feedback mechanism, but its expression and action on the LEE1 promoter are dependent on the virulence regulators Pch and Ler.
authors: Department of Biomedical Informatics, Graduate School of Medicine Osaka University, Suita, Osaka, Japan.
authors: Miyuki
authors: M
authors: Takao
authors: Hilo
authors: H
authors: Yen
authors: Toru
authors: T
authors: Tobe
mesh_terms: D001665:Binding Sites; D002087:Butyrates / Q000378:metabolism*; D054324:Enterohemorrhagic Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D051756:Leucine-Responsive Regulatory Protein / Q000378:metabolism; D009876:Operon; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D002087:Butyrates; D029968:Escherichia coli Proteins; C457340:LEE protein, E coli; C465556:Ler protein, E coli; C430340:LeuO protein, E coli; C497278:Lrp protein, E coli; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D037521:Virulence Factors; D051756:Leucine-Responsive Regulatory Protein