bEnterohemorrhagic Escherichia coli (EHEC) O157:H7 causes bloody diarrhea and hemolytic-uremic syndrome (HUS) and is the most prevalent E. coli serotype associated with food-borne illness worldwide. This pathogen is transmitted via the fecal-oral route and has a low infectious dose that has been estimated to be between 10 and 100 cells. We and others have previously identified three prophage-encoded AraC-like transcriptional regulators, PatE, PsrA, and PsrB in the EHEC O157:H7 EDL933 strain. Our analysis showed that PatE plays an important role in facilitating survival of EHEC under a number of acidic conditions, but the contribution of PsrA and PsrB to acid resistance (AR) was unknown. Here, we investigated the involvement of PsrA and PsrB in the survival of E. coli O157:H7 in acid. Our results showed that PsrB, but not PsrA, enhanced the survival of strain EDL933 under various acidic conditions. Transcriptional analysis using promoter-lacZ reporters and electrophoretic mobility shift assays demonstrated that PsrB activates transcription of the hdeA operon, which encodes a major acid stress chaperone, by interacting with its promoter region. Furthermore, using a mouse model, we showed that expression of PsrB significantly enhanced the ability of strain EDL933 to overcome the acidic barrier of the mouse stomach. Taken together, our results indicate that EDL933 acquired enhanced acid tolerance via horizontally acquired regulatory genes encoding transcriptional regulators that activate its AR machinery.
Enterohemorrhagic Escherichia coli (EHEC) strains of serotype O157:H7 are associated with epidemic and sporadic infection worldwide. EHEC is a food-and waterborne pathogen that can cause hemorrhagic colitis and hemolytic-uremic syndrome (1-4). The main reservoir of EHEC is cattle and other ruminants that shed the microorganism in feces. Many outbreaks have been associated with contaminated beef products, milk, vegetables, and fruits (5, 6). The infectious dose of EHEC is extremely low (ϳ10 to 100 cells), which significantly increases the risk of infection (7).EHEC expresses one or two cytotoxins, Shiga toxin 1 (Stx1) and/or Shiga toxin 2 (Stx2), which are responsible for the lifethreatening manifestations of infection (8, 9). In addition, EHEC (O157:H7) strains carry a pathogenicity island known as the locus of enterocyte effacement pathogenicity island (LEE PAI), which encodes portions of a type III secretion pathway, the adhesin intimin, and its translocated receptor (Tir) (10, 11). Together, these virulence factors enable EHEC to adhere to intestinal epithelial cells and form attaching-and-effacing lesions, which cause the destruction of microvilli and the rearrangement of cytoskeletal proteins (11, 12). Expression of the five operons within the LEE PAI is tightly regulated by a number of transcriptional regulators including H-NS, Ler, GrlA, integration host factor (IHF), GadE, and QseA, which allows the various virulence factors to be expressed when EHEC enters its preferred environmental niches in the host int...
