Enteropathogenic and Enterohemorrhagic Escherichia coli Virulence Gene Regulation

Biology Department, Reed College, 3203 S.E. Woodstock Boulevard, Portland, OR 97202, USA.
Infection and Immunity (Impact Factor: 3.73). 10/2007; 75(9):4199-210. DOI: 10.1128/IAI.01927-06
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Available from: Jay L Mellies, Oct 14, 2015
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    • "Chromosomal and phage encoded genetic elements also feed into the LEE creating layers of specific control on the system. Mellies et al. (2007) have previously reviewed regulation of the LEE in great detail for EHEC and EPEC. In this review, we summarize the key points of LEE regulation in relation to EHEC primarily whilst also commenting on EPEC and C. rodentium where appropriate. "
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    ABSTRACT: Enterohaemorrhagic Escherichia coli (EHEC) binds to host tissue and intimately attaches to intestinal cells using a dedicated type III secretion system (T3SS). This complex multi-protein organelle is encoded within a large pathogenicity island called the locus of enterocyte effacement (LEE), which is subject to extensive regulatory control. Over the past 15 years we have gained a wealth of knowledge concerning how the LEE is regulated transcriptionally by specific, global and phage encoded regulators. More recently, significant advances have been made in our understanding of how specific signals, including host or microbiota derived metabolic products and various nutrient sources, can affect how the LEE-encoded T3SS is regulated. In this review we discuss regulation of the LEE, focusing on how these physiologically relevant signals are sensed and how they affect the expression of this major virulence factor. The implications for understanding the disease process by specific regulatory mechanisms are also discussed.
    Frontiers in Microbiology 06/2015; 6. DOI:10.3389/fmicb.2015.00568 · 3.99 Impact Factor
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    • "LEE also encodes the transcriptional regulator Ler, which activates the transcription of other LEE genes. The expression of LEE genes is regulated in response to changes in the environmental conditions, and some responses are regulated at the LEE1 promoter, which is a promoter in the LEE1 operon, which contains the ler gene [13]. In EHEC, one of the regulatory proteins necessary for the activation of the LEE1 promoter is Pch, which is encoded by pch genes at other chromosomal loci [14], [15]. "
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    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.
    PLoS ONE 07/2014; 9(7):e101582. DOI:10.1371/journal.pone.0101582 · 3.23 Impact Factor
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    • "Our understanding of the roles of divalent metals as regulators of bacterial pathogenesis has lagged behind that of other molecules such as quorum sensing auto-inducers and transcriptional regulators such as H-NS and Ler [49]. Most of the work on transporters and metabolism of zinc and other metals has been done with non-pathogenic laboratory strains of E. coli[50-52], which makes the results difficult to extrapolate to strains which are professional intestinal or extra-intestinal pathogens. "
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    ABSTRACT: Background Zinc supplements can treat or prevent enteric infections and diarrheal disease. Many articles on zinc in bacteria, however, highlight the essential nature of this metal for bacterial growth and virulence, suggesting that zinc should make infections worse, not better. To address this paradox, we tested whether zinc might have protective effects on intestinal epithelium as well as on the pathogen. Results Using polarized monolayers of T84 cells we found that zinc protected against damage induced by hydrogen peroxide, as measured by trans-epithelial electrical resistance. Zinc also reduced peroxide-induced translocation of Shiga toxin (Stx) across T84 monolayers from the apical to basolateral side. Zinc was superior to other divalent metals to (iron, manganese, and nickel) in protecting against peroxide-induced epithelial damage, while copper also showed a protective effect. The SOS bacterial stress response pathway is a powerful regulator of Stx production in STEC. We examined whether zinc’s known inhibitory effects on Stx might be mediated by blocking the SOS response. Zinc reduced expression of recA, a reliable marker of the SOS. Zinc was more potent and more efficacious than other metals tested in inhibiting recA expression induced by hydrogen peroxide, xanthine oxidase, or the antibiotic ciprofloxacin. The close correlation between zinc’s effects on recA/SOS and on Stx suggested that inhibition of the SOS response is one mechanism by which zinc protects against STEC infection. Conclusions Zinc’s ability to protect against enteric bacterial pathogens may be the result of its combined effects on host tissues as well as inhibition of virulence in some pathogens. Research focused solely on the effects of zinc on pathogenic microbes may give an incomplete picture by failing to account for protective effects of zinc on host epithelia.
    BMC Microbiology 06/2014; 14(1):145. DOI:10.1186/1471-2180-14-145 · 2.73 Impact Factor
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