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 cups 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.
- Bacterial pathogenesis
- Bacterial virulence gene expression
- E. coli O157:H7
- Quorum sensing
- QseC mediates Salmonella enterica serovar Typhimurium virulence in vitro and in vivo.
- Moreira, C.G., Weinshenker, D. and Sperandio, V. Infection and Immunity 2010 78 914-26
- Inter-kingdom signaling: communication between bacteria and host.
- Hughes, D.T, and Sperandio, V. Nature Reviews Microbiology 2008 6 111-20
- Targeting QseC signaling and virulence for antibiotic development.
- 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. Science 2008 321 1078-1080
- The QseC sensor kinase: a bacterial adrenergic receptor.
- Clarke, M.B, Hughes, D.T., Zhu C., Boedeker, E.C. and Sperandio, V. Proc. Natl Acad. Science U.S.A. 2006 103 10420-10425
- Bacteria-host communication: the language of hormones.
- Vanessa Sperandio, Alfredo G. Torres, Bruce Jarvis, James P. Nataro, and James B. Kaper PNAS July 2003 100 8951-8956
- Chemical sensing in mammalian host-bacterial commensal associations.
- Hughes, D.T., Terekhova, D.A., Liou, L., Hovde, C.J., Sahl, J. , Patankar, A.V., Gonzalez, J.E., Edrington, T.S., Rasko, D.A., and Sperandio, V. PNAS 2010 In Press 4875-4884
- Anti-virulence strategies to combat bacteria-mediated disease
- Rasko, D.A., and Sperandio, V Nature Drug Review 2010 9 117-128
- Jamming Bacterial Communication: New Approaches for the Treatment of Infectious Diseases.
- Njoroge, J., and Sperandio, V. EMBO Molecular Medicine August 2009 1 201-210
- The QseC adrenergic signaling cascade in enterohemorrhagic E. coli (EHEC).
- Hughes, D.T., Clarke, M.B., Yamamoto, K., Rasko, D.A., and Sperandio, V. PLoS Pathogens 2009 5 e1000553
- The two-component system QseEF and the membrane protein QseG link adrenergic and stress sensing to bacterial pathogenesis.
- Reading, N.C., Rasko, R.A., Torres, A.T., and Sperandio, V. PNAS 2009 106 5889-94
Honors & Awards
- Kavli Fellow
Kavli Frontiers of Science National Academies of Science (2007)
- Burroughs Wellcome Fund
Investigator in Pathogenesis of Infectious Diseases (2006)
- Ellison Foundation Award
New Scholar of Infectious diseases (2004)
- Dam Charitable Foundation
Travel Grant (2000)
- Pew Charitable Foundation
Pew Latin american fellow (1997)