Enterococcus faecalis modulation of NF-kB signaling in macrophages

100 p.

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Main Author: Tagore, Soumili Bhaduri
Other Authors: Dr Kimberly Kline
Format: Theses and Dissertations
Language:English
Published: 2016
Subjects:
Online Access:http://hdl.handle.net/10356/69063
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-690632020-11-13T04:35:44Z Enterococcus faecalis modulation of NF-kB signaling in macrophages Tagore, Soumili Bhaduri Dr Kimberly Kline Interdisciplinary Graduate School (IGS) Singapore Center on Environmental Life Science and Engineering DRNTU::Science::Biological sciences 100 p. Enterococcus faecalis is a gram-positive commensal of the mammalian gastrointestinal tract as well as an opportunistic pathogen that can lead to endocarditis, bacteraemia, wound infections, pelvic and soft tissue infections and urinary tract infections. E. faecalis has an intrinsic and acquired resistance to several antibiotics and a high mortality rate in immune-compromised patients. It is imperative to understand how E. faecalis bacteria evade host immune response and establishes robust opportunistic infections in order to identify novel therapeutic intervention points. In this thesis, we applied a model system to study NF-κB activity in response to E. faecalis and to identify bacterial factors which modulate NF-κB activity. Employing this model system, we have shown that E. faecalis prevents NF-κB activity in murine macrophages in a dose-dependent manner and prevents NF-κB activation in response to potent activators like lipopolysaccharide and lipoteichoic acid. We established that the E. faecalis NF-κB suppressing molecule is bacterial surface-associated, heat modifiable and not secreted. We have shown that bacterial virulence factors sortase A and autolysin are important to prevent NF-κB suppression in macrophages. Furthermore, we identified a novel function for an uncharacterized sortase substrate in preventing NF-κB activity. Finally, we have identified a previously undescribed function for E. faecalis gDNA as an immunosuppresor molecule in murine immune cells. Taken together this work helps to better understand enterococcal pathogenesis and immune modulatory capability. Doctor of Philosophy (IGS) 2016-10-07T03:23:16Z 2016-10-07T03:23:16Z 2016 Thesis Tagore, S. B. (2016). Enterococcus faecalis modulation of NF-kB signaling in macrophages. Doctoral thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/69063 10.32657/10356/69063 en application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Tagore, Soumili Bhaduri
Enterococcus faecalis modulation of NF-kB signaling in macrophages
description 100 p.
author2 Dr Kimberly Kline
author_facet Dr Kimberly Kline
Tagore, Soumili Bhaduri
format Theses and Dissertations
author Tagore, Soumili Bhaduri
author_sort Tagore, Soumili Bhaduri
title Enterococcus faecalis modulation of NF-kB signaling in macrophages
title_short Enterococcus faecalis modulation of NF-kB signaling in macrophages
title_full Enterococcus faecalis modulation of NF-kB signaling in macrophages
title_fullStr Enterococcus faecalis modulation of NF-kB signaling in macrophages
title_full_unstemmed Enterococcus faecalis modulation of NF-kB signaling in macrophages
title_sort enterococcus faecalis modulation of nf-kb signaling in macrophages
publishDate 2016
url http://hdl.handle.net/10356/69063
_version_ 1688665695821234176