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dc.contributor.advisorChopra, Ashok K
dc.creatorKhajanchi, Bijay 1978-
dc.date.accessioned2016-11-01T18:12:12Z
dc.date.available2016-11-01T18:12:12Z
dc.date.created2011-08
dc.date.submittedAugust 2011
dc.identifier.urihttp://hdl.handle.net/2152.3/780
dc.description.abstractAeromonas hydrophila is a Gram-negative bacterium which produces a wide variety of virulence factors leading to both intestinal and extra-intestinal infections in humans. A large number of water and clinical Aeromonas isolates were molecularly finger-printed and our data provided the evidence of successful colonization and infection of humans with particular strains of certain Aeromonas species after consumption of water. Further, we delineated the role of N-acyl homoserine lactones (AHLs; autoinducer-1 [AI-1])-mediated quorum sensing (QS) in the virulence of a diarrheal isolate SSU of A. hydrophila by generating a ΔahyRI mutant. Our data suggested that AI-1-mediated QS modulated the in vitro virulence of A. hydrophila by regulating type 6 secretion effectors, metallo-protease production, and biofilm formation. In a septicemic mouse model, the ΔahyRI mutant was also attenuated as compared to the parental strain of A. hydrophila. In addition, we demonstrated that AHLs possess immunomodulatory and protective roles and AHL pretreatment modulates innate immune response in mice and enhances their survivability during A. hydrophila infection. Further, AHL treated animals exhibited a significantly reduced bacterial load in the blood and other mouse organs, as well as various levels of cytokines/chemokines as compared to control animals. Importantly, AHL pretreatment significantly elevated neutrophil numbers in the blood, suggesting that neutrophils quickly cleared bacteria either by phagocytosis or possibly other mechanism(s) during infection. These findings coincided with the fact that neutropenic animals were more susceptible to A. hydrophila infection than normal mice. We showed that animals challenged with A. hydrophila die because of kidney and liver damage, hypoglycemia, and thrombocytopenia, and, importantly, pretreatment of animals with AHLs prevented clinical sequelae, resulting in increased survivability of mice. Finally, we identified and characterized a new two-component based QseBC/AI-3 QS system in A. hydrophila SSU by generating a ΔqseB mutant. We noted that deletion of the qseB gene attenuated bacterial virulence in a septicemic mouse model of infection, had diminished swimming and swarming motility, and the mutant bacteria formed denser biofilms when compared to the parental strain of A. hydrophila. The decrease in the virulence of A. hydrophila ∆qseB mutant correlated with reduced production of protease and the cytotoxic enterotoxin, which has associated hemolytic activity.
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dc.subjectAeromonas hydrophila
dc.subjectquorum sensing
dc.subjectAHLs
dc.subjectQseBC
dc.subjectvirulence factors
dc.subjectbiofilm formation
dc.subjectmotility
dc.subjectT6SS
dc.subjectprotease production
dc.subjectsepticemic mouse model of infection
dc.titleEvidence of Water to Human Transmission of Aeromonas Hydrophila: Critical Role of Quorum Sensing in Bacterial Virulence & Host Response
dc.typeThesis
dc.date.updated2016-11-01T18:12:12Z
dc.type.materialtext
thesis.degree.nameMicrobiology and Immunology (Doctoral)
thesis.degree.levelDoctoral
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.departmentMicrobiology and Immunology
dc.contributor.committeeMemberPeterson, Johnny W
dc.contributor.committeeMemberSuzuki, Fujio
dc.contributor.committeeMemberMotin, Vladimir
dc.contributor.committeeMemberPancholi, Vijay


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