A. James Clark School of Engineering

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    A MATHEMATICAL MODEL TO STUDY THE ROLE OF THE LSR INTERGENIC REGION IN MEDIATION OF AUTOINDUCER-2 QUORUM SENSING IN ESCHERICHIA COLI
    (2013) Graff, Steven Meyer; Bentley, William E.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Quorum sensing (QS) is a process that allows bacteria to communicate with each other to coordinate collective behavior in response to changes in environmental conditions. Their ability to mediate biofilm formation of biofilms and antibiotic resistance has created challenges on healthcare systems, and an impetus for us to understand QS systems. QS mediated by autoinducer-2 is likely to be the most common of these mechanisms. Recent work has elaborated on the LuxS-regulated (Lsr) system which can mediate and process AI-2 to QS-dependent behaviors, particularly regulatory elements including the lsr intergenic region and the repressor LsrR, the so-called QS"switch". In this thesis, we present a simulation of an example lsr-QS-system to elucidate the role of the lsr intergenic region binding site interactions and how this model integrates with recent literature on LsrR's protein structure to provide further details on the mechanisms of how the switch may operate in real systems.
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    LOCAL AND GLOBAL GENE REGULATION ANALYSIS OF THE AUTOINDUCER-2 MEDIATED QUORUM SENSING MECHANISM IN ESCHERICHIA COLI
    (2011) Byrd, Christopher Matthew; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The term `quorum sensing' (QS) is used to define a population density based communication mechanism which uses chemical signal molecules called autoinducers to trigger unique and varied changes in gene expression. Although several communication methods have been identified in bacteria that are unique to a particular species, one type of signal molecule, autoinducer-2 (AI-2) is linked to interspecies communication, indicating its potential as a universal signal for cueing a QS response among multiple bacterial types. In E. coli, AI-2 acts as an effector by binding to the QS repressor LsrR. As a result, LsrR unbinds and relieves repression of the lsr regulon, stimulating a subsequent QS gene expression cascade. In this dissertation, LsrR structure and in vitro binding activity are examined. Genomic binding and DNA microarray analyses are conducted and three novel sites putatively regulated by LsrR, yegE-udk, mppA and yihF, are revealed. Two cAMP receptor protein (CRP) binding locations in intergenic region of the lsr regulon are also confirmed. The role of each CRP site in divergent expression is qualified, indicating the lsr intergenic region to be a class III CRP-dependent promoter. Also, four specific DNA binding sites for LsrR in the lsr intergenic region are proposed, and reliance upon simultaneous binding to these various sites and the resulting effects on LsrR repression is presented. Finally, a complex model for regulation of the lsr regulon is depicted incorporating LsrR, CRP, DNA looping, and a predicted secondary layer of repression by an integration host factor (IHF)-like protein. Further understanding of this QS genetic mechanism may potentially be used for inhibiting bacterial proliferation and infection, modifying the natural genetic system to elicit alternate desired responses, or extracted and applied to a highly customizable and sensitive in vitro biosensor.