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Transcriptional Regulation of an Exopolysaccharide Locus Required for Biofilm and Rugose Colony Formation in Vibrio vulnificus
Başlık:
Transcriptional Regulation of an Exopolysaccharide Locus Required for Biofilm and Rugose Colony Formation in Vibrio vulnificus
Yazar:
Chodur, Daniel, author. (orcid)0000-0002-9196-140X
ISBN:
9780438078901
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (201 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Dean A. Rowe-Magnus Committee members: Yves Brun; Ankur Dalia; Daniel Kearns.
Özet:
Bacteria exist in a free-living, planktonic state and in sessile, surface associated multicellular communities known as biofilms. Biofilms are of medical and industrial importance, as the resident bacteria are more resistant to environmental stressors such as antibiotics, oxidative agents and ionic stress. Our current understanding of biofilm formation restricts the development and implementation of strategies to mitigate the harmful effects caused by bacteria in a biofilm state. To alleviate the effects of biofilms caused by infectious and environmental organisms, we must examine the molecular mechanisms that control biofilm formation.
Vibrio vulnificus is a potent opportunistic human pathogen. It has the highest death rate and per case cost of any food-borne illness. Infection occurs through contact with an open wound or the ingestion of contaminated seafood. Studying biofilm formation in V. vulnificus could lead to approaches to reduce the Vibrio load in our food chain and lower the incidence of disease. My research has focused on the transcriptional regulation of an extracellular polysaccharide (EPS) required for biofilm formation and rugose development in V. vulnificus. It was known that expression of the brp-encoded EPS enhances cell-surface adherence, is regulated by c-di-GMP and requires two transcriptional regulators, BrpR and BrpT. BrpT belongs to a distinct subclass of VpsT-like regulators, which bind c-di-GMP via a conserved W[F/L/M][T/S]R motif. However, BrpT bears a proline in the third position of the c-di-GMP binding motif (WLPR) and the impact of this change on activity was unknown. I have demonstrated that the affinity of BrpT for c-di-GMP is low and that c-di-GMP binding is not a requisite for BrpT function. BrpT defines a new class of VpsT-like transcriptional regulators and the WLPR motif variant may liberate the activity of other subclass members. I have also shown that c-di-GMP and BrpT regulate the expression of an adjacent 5-gene cluster that includes the rugosity-promoting cabABC operon, brpT and another VpsT-like transcriptional regulator, brpS. BrpS represses brpA expression and is required for rugose colony development, activities that appear to depend on the ability of BrpS to bind c-di-GMP.
Lastly, I identify calcium as an environmental signal that increases intracellular c-di-GMP concentrations, which activates expression of the brp EPS and biofilm formation. I demonstrated that the production of a sulfate assimilation intermediate, 3'phospoadenosine 5'phosphosulfate (PAPS), was required for calcium-induced PbrpA expression and separately for rugose colony development. PAPS production establishes a feed-forward signaling network, where c-di-GMP and BrpT bias sulfur metabolism towards PAPS accumulation, which in turn increases c-di-GMP levels, increases brpT expression, and ultimately increases BRP polysaccharide and PAPS production. Collectively, these results contribute to our understanding of biofilm formation through elucidation of molecular mechanisms governing brp expression and requirements for biofilm formation and rugose development in V. vulnificus.
Notlar:
School code: 0093
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(694638.1) | 694638-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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