The main focus of my research is quorum sensing regulation of virulence genes in enterohemorrhagic Escherichia coli (EHEC) O157:H7. Quorum sensing is a cell-to cell signaling mechanism, in which bacteria secrete hormone-like compounds called autoinducers. When these autoinducers reach a certain threshold concentration, they interact with bacterial transcriptional regulators, regulating gene expression. The autoinducer produced by E. coli is produced by several species of bacteria, allowing intra and inter-species communication, and in EHEC quorum sensing is also used to communicate with the host. Regulation of virulence genes by quorum sensing is a relatively new concept, and the suggestion that this mechanism may also be acting in host-bacterial communication implicates that this is a way for bacteria to know when they are inside the host.
Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is the agent responsible for many outbreaks of bloody diarrhea in several countries. EHEC has a very low infectious dose and colonizes the large intestine where it causes attaching and effacing (AE) lesions and produces a potent toxin, Shiga toxin (Stx), which is responsible for the major symptoms of hemorrhagic colitis and hemolytic uremic syndrome. The AE lesion is characterized by effacement of the intestinal epithelial cell microvilli and the rearrangement of the cytoskeleton to form a pedestal-like structure that cup the bacteria individually. The genes involved in the formation of the AE lesion are encoded within a chromosomal pathogenicity island named the Locus of Enterocyte Effacement (LEE). The LEE encodes a type III secretion system, effector proteins and a bacterial adhesin. We recently reported that genes involved in the formation of the AE lesion, expression and assembly of flagella, motility and Shiga toxin expression were regulated by quorum sensing (Sperandio et al., 1999; Sperandio et al., accepted). Indicating that quorum sensing plays an important role in EHEC pathogenesis.
Our laboratory is interested in trying to identify and understand the regulatory cascade involved in quorum sensing regulation of virulence genes in EHEC. We are also studying the nature of the interactions between the bacterial autoinducer and the host signals, and how these compounds regulate bacterial virulence gene expression and whether they also have any effect in epithelial cells. Further understanding of this regulatory system will lead to the identification of additional virulence factors and provide novel targets for vaccine and drug development.
RESEARCH INTERESTS
Bacterial virulence gene expression
Quorum sensing
E. coli O157:H7
Bacterial pathogenesis
Biofilms
RECENT PUBLICATIONS
Rasko, D.A., Moreira, C.G., Li, D.R., Reading, N.C., Ritchie, J.M., Waldor, M.K., Williams, N. Taussig, R., Wei, S., Roth, M. Hughes, D.T., Huntley, J.F., Fina, M.W., Falck, J.R., Sperandio, V., "Targeting QseC signaling and virulence for antibiotic development." Science, 321:1078-1080, August 2008
Hughes, D.T, and Sperandio, V., "Inter-kingdom signaling: communication between bacteria and host." Nature Reviews Microbiology, 6:111-20, 2008
Reading, N.C., Torres, A.T., Kendall, M.M., Hughes, D.T., Yamamoto, K. and Sperandio, V., "A novel two-component system that activates transcription of an enterohemorrhagic E. coli (EHEC) effector involved in remodeling of host actin." Journal Bacteriology, 189:2468-2476, 2007
Kendall, M.N., Rasko D.A., and Sperandio, V., "Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2, Autoinducer-3, and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli." Infection and Immunity, 75:4875-4884, 2007
Sharp, F.C., and Sperandio, V., "QseA directly activates transcription of LEE1 in enterohemorrhagic E. coli (EHEC)." Infection and Immunity, 75:2432-2440, 2007
SIGNIFICANT PUBLICATIONS
Vanessa Sperandio, Alfredo G. Torres, Bruce Jarvis, James P. Nataro, and James B. Kaper, "Bacteria-host communication: the language of hormones." PNAS, 100:8951-8956, July 2003
Clarke, M.B, Hughes, D.T., Zhu C., Boedeker, E.C. and Sperandio, V., "The QseC sensor kinase: a bacterial adrenergic receptor." Proc. Natl Acad. Science U.S.A., 103:10420-10425, 2006
Walters, M., Sircili, M.P., and Sperandio, V., "AI-3 synthesis is not dependent on luxS in E. coli." Journal of Bacteriology, 188:5668-5681, 2006
Clarke, M.B. and Sperandio, V., "Transcriptional regulation of flhDC by QseBC and 28 (FliA) in EHEC." Molecular Microbiology, 57:1734-1749, 2005
Clarke, M.B., and Sperandio V., "Transcriptional autoregulation by quorum sensing E. coli regulators B and C (QseBC) in enterohemorrhagic E. coli (EHEC)." Molecular Microbiology, 58:441-455, 2005
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