Enterohemorrhagic E. coli (EHEC) serotype O157:H7 is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome throughout the world. The main reservoir for EHEC is cattle herds. EHEC colonization of cattle has been shown to require a functional locus of enterocyte effacement (LEE) region, involved in intestinal adhesion, and formation of lesions on enterocytes named attaching and effacing (AE) lesions, as well as a functional SdiA transcription factor. SdiA is a quorum sensing transcription factor that requires its autoinducer, an acyl-homoserine lactone (AHL) for proper folding and function. EHEC harbors SdiA, but does not produce an AHL autoinducer, consequently having to sense AHLs produced by other species of bacteria in the environment. These observations, combined with reports showing that AHLs are prominent within cattle rumen, suggest an important role for SdiA- AHL mediated regulation of EHEC genes necessary for colonization of the bovine gastrointestinal (GI) tract. We demonstrated that both synthetic AHLs, as well as AHLs extracted from cattle rumen repress expression of the LEE genes. However, the role of diet in modulating AHL levels within the rumen, and their correlation with EHEC shedding remain poorly understood. Furthermore, the mechanisms by which SdiA regulates transcription are still unknown. Finally, the distribution of an sdiA mutant within the intestinal tract of cattle, as well as a definitive reason underlying its attenuation remains to be established. Accordingly the Specific Aims of this study are:
Specific Aim 1 : To assess the presence of AHLs in rumen samples from cattle, as well as their correlation with diet and EHEC shedding.
Specific Aim 2 : Determine the molecular mechanisms of SdiA-dependent gene regulation.
Specific Aim 3 : Characterize the distribution of an sdiA mutant within the bovine intestine, and better define the basis for this mutant's diminished ability to colonize cattle.
Enterohemorrhagic E.coli (EHEC) serotype O157:H7 is the agent responsible for outbreaks of bloody diarrhea throughout the world. The main reservoir for EHEC is cattle herds. Consequently, diminishing cattle colonization and shedding of EHEC is of great interest to human health. In this grant proposal, we aim to understand how a signaling mechanism between bacterial cells through a small molecule called acyl-homoserine lactone, which is present in the rumen of cattle, controls expression of EHEC genes necessary for virulence and colonization of the bovine intestine.
|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:|
|Carlson-Banning, Kimberly M; Sperandio, Vanessa (2017) Enterohemorrhagic Escherichia coli outwits hosts through sensing small molecules. Curr Opin Microbiol 41:83-88|
|Kendall, Melissa M; Sperandio, Vanessa (2016) What a Dinner Party! Mechanisms and Functions of Interkingdom Signaling in Host-Pathogen Associations. MBio 7:e01748|
|Bäumler, Andreas J; Sperandio, Vanessa (2016) Interactions between the microbiota and pathogenic bacteria in the gut. Nature 535:85-93|
|Cameron, Elizabeth A; Sperandio, Vanessa (2015) Frenemies: Signaling and Nutritional Integration in Pathogen-Microbiota-Host Interactions. Cell Host Microbe 18:275-84|
|Nguyen, Y; Nguyen, Nam X; Rogers, Jamie L et al. (2015) Structural and mechanistic roles of novel chemical ligands on the SdiA quorum-sensing transcription regulator. MBio 6:|
|Sperandio, Vanessa (2015) Bacterial Reductionism: Host Thiols Enhance Virulence. Cell Host Microbe 18:7-8|
|Curtis, Meredith M; Hu, Zeping; Klimko, Claire et al. (2014) The gut commensal Bacteroides thetaiotaomicron exacerbates enteric infection through modification of the metabolic landscape. Cell Host Microbe 16:759-69|
|Gruber, Charley C; Sperandio, Vanessa (2014) Posttranscriptional control of microbe-induced rearrangement of host cell actin. MBio 5:e01025-13|
|Njoroge, Jacqueline W; Gruber, Charley; Sperandio, Vanessa (2013) The interacting Cra and KdpE regulators are involved in the expression of multiple virulence factors in enterohemorrhagic Escherichia coli. J Bacteriol 195:2499-508|
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