title: Antisense transcription regulates the expression of the enterohemorrhagic Escherichia coli virulence regulatory gene ler in response to the intracellular iron concentration.
abstract: Enteric pathogens, such as enterohemorrhagic E. coli (EHEC) O157:H7, encounter varying concentrations of iron during their life cycle. In the gastrointestinal tract, the amount of available free iron is limited because of absorption by host factors. EHEC and other enteric pathogens have developed sophisticated iron-responsive systems to utilize limited iron resources, and these systems are primarily regulated by the Fur repressor protein. The iron concentration could be a signal that controls gene expression in the intestines. In this study, we explored the role of iron in LEE (locus for enterocyte effacement) virulence gene expression in EHEC. In contrast to the expression of Fur-regulated genes, the expression of LEE genes was greatly reduced in fur mutants irrespective of the iron concentration. The expression of the ler gene, the LEE-encoded master regulator, was affected at a post-transcription step by fur mutation. Further analysis showed that the loss of Fur affected the translation of the ler gene by increasing the intracellular concentration of free iron, and the transcription of the antisense strand was necessary for regulation. The results indicate that LEE gene expression is closely linked to the control of intracellular free iron homeostasis.
authors.affiliation: Department of Biomedical Informatics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Tobe
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hilo
authors.initials: H
authors.lastname: Yen
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kagayama
authors.affiliation: Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Naotake
authors.initials: N
authors.lastname: Ogasawara
authors.affiliation: Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Oshima
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D019453:Escherichia coli O157 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D005293:Ferritins / Q000502:physiology; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism*; D020320:Oligoribonucleotides, Antisense / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013308:Streptonigrin / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C457340:LEE protein, E coli; C465556:Ler protein, E coli; D020320:Oligoribonucleotides, Antisense; D010750:Phosphoproteins; D012097:Repressor Proteins; D015534:Trans-Activators; C068477:ferric uptake regulating proteins, bacterial; D013308:Streptonigrin; D005293:Ferritins; D007501:Iron