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Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system. / Rand Jihad AL-Ishaq

Swansea University Author: Rand Jihad AL-Ishaq

Abstract

Synthesis of polysaccharide intercellular adhesin (PIA), accumulation associated protein (Aap) and extracellular matrix binding protein (Embp) are major mechanisms used by Staphylococcus epidermidisto evade immunity through biofilm formation. These evasion strategies are particularly suited for colo...

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Published: 2013
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42878
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last_indexed 2019-10-21T16:48:37Z
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spelling 2018-08-29T14:27:29.8749842 v2 42878 2018-08-02 Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system. c2dae48352cb9d9361eaf88dcaeed11c NULL Rand Jihad AL-Ishaq Rand Jihad AL-Ishaq true true 2018-08-02 Synthesis of polysaccharide intercellular adhesin (PIA), accumulation associated protein (Aap) and extracellular matrix binding protein (Embp) are major mechanisms used by Staphylococcus epidermidisto evade immunity through biofilm formation. These evasion strategies are particularly suited for colonisation of medical devices such as heart valves, joint prostheses and central venous catheters resulting in significant patient morbidity. Two biological activities of PIA, Aap and Embp contribute to their role as an evasion molecules. Firstly their ‘barrier’ function limiting penetration of immune cells and antibiotics. Secondly, their ‘immunomodulatory’ properties which influence cytokine responses. At present little is known about these functional activities in physiological media and biological fluids.This thesis uses a cell biology approach to study the environment necessary for PLA production. Specifically in vitromodelling of biofilm formation, PIA production and S. epidermidisleukocyte co-culture experiments have been used to assess conditions that are conducive for PIA production.This thesis has identified that:• Specific cell culture media cause unique profiles of biofilm accumulation with differential production of PIA, Aap and Embp.• Fetal bovine serum and pooled human serum support S. epidermidisgrowth but differentially affect biofilm formation by PIA, Aap and Embp.• Large scale production of PIA (~20mg) can be achieved by culturing in Iscove's Modified Dulbecco's Media which has allowed streamlining of current isolation procedures.• PIA induction of cytokines, including IL-8 and TNF is dependent on being tethered to the bacterial membrane.• Macrophages can penetrate into a S. epidermidisproduced PIA ‘barrier’.• Immunosuppression of whole blood with dexamethasone unmasks the pathogenic advantage of PIA in S. epidermidisexpressing PIA compared to negative controls.• Whole blood killing of S. epidermidisis dependent on CD1 lb/CD 18.• PIA induces whole blood killing dysfunction which is likely related to C5a production.• PIA can be produced in a whole blood environment.• Inocula of -1 0 colony forming unit of S. epidermidisare required to form biofilms in whole blood.This study suggests the importance of studying clinically important biofilm production mechanisms under conditions that closely resemble those in human disease. E-Thesis Staph infections 31 12 2013 2013-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T14:27:29.8749842 2018-08-02T16:24:30.6950111 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Rand Jihad AL-Ishaq NULL 1 0042878-02082018162528.pdf 10821268.pdf 2018-08-02T16:25:28.9470000 Output 16523509 application/pdf E-Thesis true 2018-08-02T16:25:28.9470000 false
title Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
spellingShingle Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
Rand Jihad AL-Ishaq
title_short Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
title_full Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
title_fullStr Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
title_full_unstemmed Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
title_sort Functional role of polysaccharide intercellular adhesin during Staphylococcus epidermidis biofilm interaction with the innate immune system.
author_id_str_mv c2dae48352cb9d9361eaf88dcaeed11c
author_id_fullname_str_mv c2dae48352cb9d9361eaf88dcaeed11c_***_Rand Jihad AL-Ishaq
author Rand Jihad AL-Ishaq
author2 Rand Jihad AL-Ishaq
format E-Thesis
publishDate 2013
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Synthesis of polysaccharide intercellular adhesin (PIA), accumulation associated protein (Aap) and extracellular matrix binding protein (Embp) are major mechanisms used by Staphylococcus epidermidisto evade immunity through biofilm formation. These evasion strategies are particularly suited for colonisation of medical devices such as heart valves, joint prostheses and central venous catheters resulting in significant patient morbidity. Two biological activities of PIA, Aap and Embp contribute to their role as an evasion molecules. Firstly their ‘barrier’ function limiting penetration of immune cells and antibiotics. Secondly, their ‘immunomodulatory’ properties which influence cytokine responses. At present little is known about these functional activities in physiological media and biological fluids.This thesis uses a cell biology approach to study the environment necessary for PLA production. Specifically in vitromodelling of biofilm formation, PIA production and S. epidermidisleukocyte co-culture experiments have been used to assess conditions that are conducive for PIA production.This thesis has identified that:• Specific cell culture media cause unique profiles of biofilm accumulation with differential production of PIA, Aap and Embp.• Fetal bovine serum and pooled human serum support S. epidermidisgrowth but differentially affect biofilm formation by PIA, Aap and Embp.• Large scale production of PIA (~20mg) can be achieved by culturing in Iscove's Modified Dulbecco's Media which has allowed streamlining of current isolation procedures.• PIA induction of cytokines, including IL-8 and TNF is dependent on being tethered to the bacterial membrane.• Macrophages can penetrate into a S. epidermidisproduced PIA ‘barrier’.• Immunosuppression of whole blood with dexamethasone unmasks the pathogenic advantage of PIA in S. epidermidisexpressing PIA compared to negative controls.• Whole blood killing of S. epidermidisis dependent on CD1 lb/CD 18.• PIA induces whole blood killing dysfunction which is likely related to C5a production.• PIA can be produced in a whole blood environment.• Inocula of -1 0 colony forming unit of S. epidermidisare required to form biofilms in whole blood.This study suggests the importance of studying clinically important biofilm production mechanisms under conditions that closely resemble those in human disease.
published_date 2013-12-31T03:53:49Z
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score 11.03559

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