Characterizing the AbcR/VtlR system in the Rhizobiales

dc.contributor.authorSheehan, Lauren Marieen
dc.contributor.committeechairCaswell, Clayton C.en
dc.contributor.committeememberInzana, Thomas Josephen
dc.contributor.committeememberSriranganathan, Nammalwaren
dc.contributor.committeememberScharf, Birgit E.en
dc.contributor.departmentBiomedical and Veterinary Sciencesen
dc.date.accessioned2020-01-22T07:00:32Zen
dc.date.available2020-01-22T07:00:32Zen
dc.date.issued2018-07-30en
dc.description.abstractRhizobiales encompass a diverse group of microbes, ranging from free-living, soil-dwelling bacteria to disease-causing, intracellular pathogens. Although the lifestyle of these organisms vary, many genetic systems are well conserved. One system, named the AbcR/VtlR system, is found throughout rhizobiales, and even extends to bacteria in other orders within the Alphaproteobacteria. The AbcR sRNAs are an example of sibling sRNAs, where two copies of the abcR gene are typically present in the genome. The AbcRs are involved in the negative regulation of ABC-type transport systems, which are important components for nutrient acquisition. Although the AbcRs share several features amongst organisms, major differences can be found in their functional and regulatory redundancy, the targets they regulate and how they regulate them. Specifically, one major difference in the AbcRs lies in the nucleotide sequences utilized by the sRNAs to bind mRNA targets. In the present studies, the regulatory mechanisms of the AbcR sRNAs were further characterized in the mammalian pathogen Brucella abortus, and the full regulatory profiles of the AbcRs were defined in the plant pathogen Agrobacterium tumefaciens. As mentioned above, the AbcR sRNAs are important for the proper regulation of nutrient-acquiring transport systems in the Rhizobiales. Since these sRNAs are critical to the lifestyle of a bacterium, proper regulation of this system is key to survival. A LysR-type transcriptional regulator, named VtlR, was found to be the bonefide transcriptional activator of abcR1 in B. abortus. Furthermore, VtlR has been shown to be a key component in host interactions in several rhizobiales. The preset work has shed light on the evolutionary divergence of this regulator in bacteria, and further defined the regulatory capacity of VtlR in Agrobacterium. Overall, the studies described here have made significant advances in our knowledge of the AbcR/VtlR-regulatory systems in the Rhizobiales, and have further defined this system as being a vital part of host-microbe interactions.en
dc.description.abstractgeneralUnderstanding the genetic systems utilized by microbes to cause infection is key for developing therapeutics that can be administered to fight against them. Moreover, identifying and characterizing these essential microbial systems can be exploited for the development of drugs to target and shut down these systems, thus causing cell death. The present work took a basic molecular biology approach and characterized a highly conserved genetic system, named the AbcR/VtlR system, in two pathogenic bacteria: the plant pathogen Agrobacterium and the mammalian pathogen Brucella. Overall, the work described here shows this system to be an important component in acquiring nutrients for the microbe, and, most importantly, found the AbcR/VtlR system to be essential for host-microbial interactions.en
dc.description.degreePHDen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:15504en
dc.identifier.urihttp://hdl.handle.net/10919/96536en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectBrucellaen
dc.subjectLysR-type transcriptional regulatorsen
dc.subjectsmall RNAsen
dc.titleCharacterizing the AbcR/VtlR system in the Rhizobialesen
dc.typeDissertationen
thesis.degree.disciplineBiomedical and Veterinary Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePHDen

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