Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus

Streptococcus gallolyticus subsp. gallolyticus is an emerging pathogen responsible for infective endocarditis especially in the elderly. Many infected patients were found to exhibit a condition of concomitant colorectal neoplasia; therefore colonoscopy is now advised for S. gallolyticus-infected pat...

Full description

Saved in:
Bibliographic Details
Main Author: Teh, Wooi Keong
Other Authors: Liang Zhao-Xun
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2019
Subjects:
Online Access:https://hdl.handle.net/10356/136501
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-136501
record_format dspace
spelling sg-ntu-dr.10356-1365012020-11-01T04:53:59Z Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus Teh, Wooi Keong Liang Zhao-Xun Interdisciplinary Graduate School (IGS) Singapore Centre for Environmental Life Sciences and Engineering ZXLiang@ntu.edu.sg Science::Biological sciences Streptococcus gallolyticus subsp. gallolyticus is an emerging pathogen responsible for infective endocarditis especially in the elderly. Many infected patients were found to exhibit a condition of concomitant colorectal neoplasia; therefore colonoscopy is now advised for S. gallolyticus-infected patients to screen for the presence of early stage colorectal tumours. It has been recently proposed that S. gallolyticus subsp. gallolyticus plays an auxiliary role in colorectal cancer development, albeit the detailed mechanisms allowing S. gallolyticus subsp. gallolyticus to promote the tumorous cells progression remains unidentified. Previous studies suggested that bacterial biofilms residing in the gastrointestinal tract may play a role in the colorectal cancer development. In this dissertation, the primary objective was to understand S. gallolyticus subsp. gallolyticus biofilm biology, for the interest of further investigations on the roles of S. gallolyticus subsp. gallolyticus biofilms in colorectal cancer development. I first provide evidence that S. gallolyticus subsp. gallolyticus biofilm development is controlled by the bacterial second messenger cyclic diadenosine-monophosphate (c-di-AMP). It was found that the deletion mutant (∆gdpP) of the c-di-AMP specific phosphodiesterase GdpP accumulating higher intracellular level of c-di-AMP displayed defect in biofilm development. Further investigations focusing on the molecular mechanisms of c-di-AMP control on S. gallolyticus subsp. gallolyticus biofilm development revealed that the expression of the extracellular pullulanase PulA and the extracellular appendage pili Pil3 is responsive to the intracellular c-di-AMP level. Both the reduced expression of PulA and Pil3 contribute in part to biofilm developmental defect of the S. gallolyticus subsp. gallolyticus ∆gdpP mutant. In view of the numerous studies that have indicated c-di-AMP to play a primary role in controlling bacterial osmotic homeostasis, the S. gallolyticus subsp. gallolyticus ∆gdpP mutant was characterised. It was found that the mutant cells were more sensitive to high osmotic stress and were smaller in cell size compared to the parental strain. It was also found that the expression of various transporters involved in controlling the uptake of osmolytes was down-regulated in the ∆gdpP mutant compared with the parental strain. Collectively, the present PhD thesis supports the notion that c-di-AMP plays a conserved role in maintaining osmotic homeostasis in many Gram-positive bacteria and establishes that c-di-AMP is a bona fide signalling molecule controlling S. gallolyticus subsp. gallolyticus biofilm development. Doctor of Philosophy 2019-12-20T05:04:49Z 2019-12-20T05:04:49Z 2019 Thesis-Doctor of Philosophy Teh, W. K. (2019). Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/136501 10.32657/10356/136501 en application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
spellingShingle Science::Biological sciences
Teh, Wooi Keong
Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus
description Streptococcus gallolyticus subsp. gallolyticus is an emerging pathogen responsible for infective endocarditis especially in the elderly. Many infected patients were found to exhibit a condition of concomitant colorectal neoplasia; therefore colonoscopy is now advised for S. gallolyticus-infected patients to screen for the presence of early stage colorectal tumours. It has been recently proposed that S. gallolyticus subsp. gallolyticus plays an auxiliary role in colorectal cancer development, albeit the detailed mechanisms allowing S. gallolyticus subsp. gallolyticus to promote the tumorous cells progression remains unidentified. Previous studies suggested that bacterial biofilms residing in the gastrointestinal tract may play a role in the colorectal cancer development. In this dissertation, the primary objective was to understand S. gallolyticus subsp. gallolyticus biofilm biology, for the interest of further investigations on the roles of S. gallolyticus subsp. gallolyticus biofilms in colorectal cancer development. I first provide evidence that S. gallolyticus subsp. gallolyticus biofilm development is controlled by the bacterial second messenger cyclic diadenosine-monophosphate (c-di-AMP). It was found that the deletion mutant (∆gdpP) of the c-di-AMP specific phosphodiesterase GdpP accumulating higher intracellular level of c-di-AMP displayed defect in biofilm development. Further investigations focusing on the molecular mechanisms of c-di-AMP control on S. gallolyticus subsp. gallolyticus biofilm development revealed that the expression of the extracellular pullulanase PulA and the extracellular appendage pili Pil3 is responsive to the intracellular c-di-AMP level. Both the reduced expression of PulA and Pil3 contribute in part to biofilm developmental defect of the S. gallolyticus subsp. gallolyticus ∆gdpP mutant. In view of the numerous studies that have indicated c-di-AMP to play a primary role in controlling bacterial osmotic homeostasis, the S. gallolyticus subsp. gallolyticus ∆gdpP mutant was characterised. It was found that the mutant cells were more sensitive to high osmotic stress and were smaller in cell size compared to the parental strain. It was also found that the expression of various transporters involved in controlling the uptake of osmolytes was down-regulated in the ∆gdpP mutant compared with the parental strain. Collectively, the present PhD thesis supports the notion that c-di-AMP plays a conserved role in maintaining osmotic homeostasis in many Gram-positive bacteria and establishes that c-di-AMP is a bona fide signalling molecule controlling S. gallolyticus subsp. gallolyticus biofilm development.
author2 Liang Zhao-Xun
author_facet Liang Zhao-Xun
Teh, Wooi Keong
format Thesis-Doctor of Philosophy
author Teh, Wooi Keong
author_sort Teh, Wooi Keong
title Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus
title_short Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus
title_full Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus
title_fullStr Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus
title_full_unstemmed Investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (C-DI-AMP) in streptococcus gallolyticus subsp. gallolyticus
title_sort investigation on the regulatory roles of a second messenger cyclic diadenosine-monophosphate (c-di-amp) in streptococcus gallolyticus subsp. gallolyticus
publisher Nanyang Technological University
publishDate 2019
url https://hdl.handle.net/10356/136501
_version_ 1683493732726341632