The Type Three Secretion System 2-Encoded Regulator EtrB Modulates Enterohemorrhagic Escherichia coli Virulence Gene Expression.
Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a foodborne pathogen that causes bloody diarrhea and hemolytic uremic syndrome throughout the world. A defining feature of EHEC pathogenesis is the formation of attaching and effacing (AE) lesions on colonic epithelial cells. Most of the genes that code for AE lesion formation, including a type three secretion system (T3SS) and effectors, are carried within a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE). In this study, we report that a putative regulator, which is encoded in the cryptic E. coli type three secretion system 2 (ETT2) locus and herein renamed EtrB, plays an important role in EHEC pathogenesis. The etrB gene is expressed as a monocistronic transcript, and EtrB autoregulates expression. We provide evidence that EtrB directly interacts with the ler regulatory region to activate LEE expression and promote AE lesion formation. Additionally, we mapped the EtrB regulatory circuit in EHEC to determine a global role for EtrB. EtrB is regulated by the transcription factor QseA, suggesting that these proteins comprise a regulatory circuit important for EHEC colonization of the gastrointestinal tract.
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Deborah H
DH
Luzader
Department of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, Vermont, USA.
Graham G
GG
Willsey
Department of Microbiology and Molecular Genetics, University of Vermont College of Medicine, Burlington, Vermont, USA.
Matthew J
MJ
Wargo
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA melissakendall@virginia.edu.
Melissa M
MM
Kendall
D003106:Colon / Q000382:microbiology; D054324:Enterohemorrhagic Escherichia coli / Q000235:genetics*; D019453:Escherichia coli O157 / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D000069296:Type III Secretion Systems / Q000235:genetics*; D014774:Virulence / Q000235:genetics*
D029968:Escherichia coli Proteins; D014157:Transcription Factors; D000069296:Type III Secretion Systems