The Characterization of Quorum Sensing E. Coli Regulators E,F, and G (Qse EFG) and Their Role in Pathogenesis
Reading, Nicola Catherine
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Escherichia coli O157:H7 (EHEC) causes hemorrhagic colitis and life-threatening hemolytic uremic syndrome (HUS) worldwide. EHEC colonizes the large intestine and adheres to intestinal epithelial cells by forming attaching and effacing lesions (AE). These lesions result in the rearrangement of the actin cytoskeleton 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 protein, Tir, and the outer membrane protein, Intimin. Also, a prophage encoded effector protein, EspFu, is required. EHEC regulates many of its virulence genes including the AE lesion genes in response to environmental signals. Utilizing these signals allows EHEC to colonize the intestine efficiently and effectively. Environmental signals are often recognized by bacterial sensor kinases. In response to cognate signals, sensor kinases autophosphorylate and transfer the phosphate to a response regulator. The regulator then binds downstream genes to regulate transcription. This pathway for flagellation and motility, which allows EHEC to be motile, has been well-characterized and involves the two-component sytem QseBC. 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 regulators 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 and stress. The similar profiles of these mutants in the microarray indicate that these proteins may work together. QseE is able to autophosphorylate and this activity is stimulated by epinephrine, phosphate, and sulfate sources. These data indicate that QseEFG is a three-component system involved in regulation of virulence and metabolism in EHEC. The following study undertakes a genetic and functional analysis of these proteins.