- Taschenbuch: 148 Seiten
- Verlag: Proquest, Umi Dissertation Publishing (September 2011)
- Sprache: Englisch
- ISBN-10: 1243587369
- ISBN-13: 978-1243587367
- Größe und/oder Gewicht: 24,6 x 18,9 x 0,8 cm
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Kurzbeschreibung
Communities of bacteria coordinate the regulation of genes at high cell density to adapt to changing environments. In Proteobacteria a form gene regulation called quorum sensing uses diffusible acyl-homoserine lactones (acyl-HSLs) to modulate gene expression. Acyl-HSLs are catalyzed by enzymes belonging to the LuxI family of acyl-HSL synthases. At elevated concentrations acyl-HSLs bind to and activate LuxR family transcription factors. Many bacteria use quorum sensing to regulate gene expression, including virulence and secondary metabolic genes. Burkholderia mallei and Burkholderia thailandensis are close genetic relatives that occupy distinct habitats. B. mallei is an obligate mammalian parasite and causes disease. B. thailandensis is a soil saprophyte and rarely causes disease. Their genomes encode five related luxR and luxI type quorum-sensing genes whose products are ≥98% identical at the amino acid level. The B. thailandensis genome also has a luxR and luxI gene that is absent form the B. mallei chromosome. In B. mallei quorum sensing has been implicated in virulence. Little is known about the acyl-HSL signals produced by these bacteria and what genes their LuxR receptors regulate. The goal of my research was to identify the B. mallei and B. thailandensis acyl-HSLs and their cognate LuxR receptors and further characterize the genes regulated by these systems. Both organisms produce N-octanoyl-HSL (C8-HSL) and N-3-hydroxy-octanoyl-HSL (3OHC8-HSL) via the Bmal1-Bmal3 and Btal1-Btal3 synthases respectively. B. thailandensis produces a third acyl-HSL, N-3-hydroxy-decanoyl-HSL (3OHC10-HSL), which is the product of the Btal2 acyl-HSL synthase. In B. mallei the LuxR receptors BmaR1 and BmaR3 bind C8-HSL and 3OHC8-HSL respectively. B. mallei activates bmaI1 transcription in response to both C8-HSL and 3OHC8-HSL. A recombinant screen for BmaR1-C8-HSL controlled genes also revealed two loci regulated by BmaR-BmaI1. In B. thailandensis BtaR2 responds to 3OHC10-HSL and regulates genes involved in antibiotic production. At least one of these antibiotics has activity against Gram-positive bacteria. This dissertation provides evidence that quorum sensing is an important component of the physiological response in both B. mallei and B. thailandensis and is the starting point to gain insight into the role of quorum sensing during pathogenesis and environmental adaptation.
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