B-176. Quorum Sensing E. coli Regulators E, F, and G (QseEFG): a Three Component System Important for Enterohemorrhagic E. coli (EHEC) Pathogenesis

N. C. Reading¹, A. G. Torres², K. Yamamoto³, V. Sperandio¹;
¹Univ. of Texas Southwestern Med. Ctr., Dallas, TX, ²Univ. of Texas Med. Branch, Galveston, TX, ³Kinki Univ., Nakamachi, Nara, JAPAN.

Escherichia coli O157:H7 (EHEC) causes hemorrhagic colitis and life threatening hemolytic uremic syndrome (HUS) worldwide. EHEC colonizes the large intestine and tightly adheres to intestinal epithelial cells by forming attaching and effacing lesions (AE). These lesions result in the rearrangement of the actin cytoskeleton leading to pedestal-like structures, which cup each bacterium. The genes necessary for formation of pedestals are encoded in the Locus of Enterocyte Effacement (LEE), including a type III secretion system, an effector, Tir, and the outer membrane protein, Intimin. Also, a prophage encoded protein, EspFu, is required. EHEC regulates many of its virulence genes including the AE lesion formation genes in response to environmental signals. These signals are often recognized by sensor kinases. In response to specific cues, sensor kinases autophosphorylate and transfer the phosphate to a response regulator. The regulator then binds downstream genes to regulate transcription. This pathway for flagella and motility has been well-characterized, but less is known about the signaling towards EHEC’s AE lesion formation capability. Here, we describe a unique signaling system important for EHEC pedestal formation. In contrast to conventional two-component signaling systems, this one consists of three-components. Quorum sensing E.coli regulator E (qseE), qseG, and qseF encode a sensor kinase, membrane protein, and response regulator respectively. qseF and qseG mutant strains cannot form pedestals on epithelial cells. We have shown that QseF transcriptionally regulates espFu. When espFu is expressed on a plasmid, pedestal formation is restored to the qseF mutant. Microarray analysis comparing qseE, qseF, and qseG mutants to wild type revealed that these genes may also play a role in metabolism. The similar profiles of these mutants in the microarray indicate that these proteins work together. Initial tests show that epinephrine, nitrogen, and phosphate sources activate QseE. These data indicate that QseEFG is a three-component system involved in regulation of virulence and metabolism in EHEC.