EXCEED THE SPACE PROVIDED. Enterohemorrhagic E. coli (EHEC) O157:H7 causes bloody diarrhea and hemolytic uremic syndrome (HUS) throughout the world. EHEC has a very low infectious dose, making it difficult to control epidemiologically. EHEC colonizes the large intestine where it causes attaching and effacing (AE) lesions, and also produces Shiga toxins (Stx) that are responsible for the major symptoms of HUS. Although the virulence mechanisms of EHEC have been extensively studied, very little is known about how EHEC regulates the expression of its virulence genes. We recently reported that both of the genes involved in AE lesion formation, as well as Stx production, are activated by quorum sensing (QS). QS is a cell-to-cell signaling mechanism in which bacteria secrete hormone-like compounds (autoinducers) that interact with bacterial transcriptional regulators to drive gene expression. The QS mechanism employed in this activation is primarily involved in bacterial inter-species communication, and we propose that activation of EHEC virulence genes by this system would occur in response to autoinducers produced by the normal intestinal flora (which could be an explanation for its low infectious dose). This proposal represents a comprehensive effort to study virulence gene regulation in EHEC.
In Specific Aim 1, we shall identify other previously uncharacterized EHEC-specific QS regulated genes. Given that QS regulation is critical for EHEC pathogenesis, the identification of such genes expressed in concert with known virulence factors may lead to the discovery of novel virulence genes.
In Specific Aim 2, we shall identify and characterize the transcriptional regulators of the QS regulon.
Specific Aim 3 is designed to address the role of QS not only in bacterial-bacterial but also bacterial-host cell communication, and monitor QS virulence gene regulation 'in vivo'. The proposed experimental approaches will achieve a better understanding of the sensory events by which EHEC responds to activate its virulence genes, and may lead to the identification of other virulence genes and novel targets for the potential development of more effective intervention strategies for EHEC disease. PERFORMANCE SITE ========================================Section End===========================================
|Cameron, Elizabeth A; Curtis, Meredith M; Kumar, Aman et al. (2018) Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic Escherichia coli. MBio 9:|
|Cameron, Elizabeth A; Gruber, Charley C; Ritchie, Jennifer M et al. (2018) The QseG Lipoprotein Impacts the Virulence of Enterohemorrhagic Escherichia coli and Citrobacter rodentium and Regulates Flagellar Phase Variation in Salmonella enterica Serovar Typhimurium. Infect Immun 86:|
|Pifer, Reed; Russell, Regan M; Kumar, Aman et al. (2018) Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut. Proc Natl Acad Sci U S A 115:E10712-E10719|
|Carlson-Banning, Kimberly M; Sperandio, Vanessa (2018) Enterohemorrhagic Escherichia coli outwits hosts through sensing small molecules. Curr Opin Microbiol 41:83-88|
|Hernandez-Doria, Juan D; Sperandio, Vanessa (2018) Bacteriophage Transcription Factor Cro Regulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli. Cell Host Microbe 23:607-617.e6|
|Parker, Christopher T; Russell, Regan; Njoroge, Jacqueline W et al. (2017) Genetic and Mechanistic Analyses of the Periplasmic Domain of the Enterohemorrhagic Escherichia coli QseC Histidine Sensor Kinase. J Bacteriol 199:|
|Moreira, Cristiano G; Russell, Regan; Mishra, Animesh Anand et al. (2016) Bacterial Adrenergic Sensors Regulate Virulence of Enteric Pathogens in the Gut. MBio 7:|
|Carlson-Banning, Kimberly M; Sperandio, Vanessa (2016) Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence. MBio 7:|
|Bäumler, Andreas J; Sperandio, Vanessa (2016) Interactions between the microbiota and pathogenic bacteria in the gut. Nature 535:85-93|
|Kendall, Melissa M; Sperandio, Vanessa (2016) What a Dinner Party! Mechanisms and Functions of Interkingdom Signaling in Host-Pathogen Associations. MBio 7:e01748|
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