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Title: Oral ecosystem modulation and bacterial pneumonia
Author: Twigg, Joshua
ISNI:       0000 0004 9347 5282
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2019
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Bacterial pneumonia affects a disproportionate number of elderly in the UK, with substantial morbidity and mortality. Mounting evidence implicates removable dentures as a potential nidus for respiratory pathogens to form a pathogenic reservoir which could seed colonisation and infection of respiratory tissues in susceptible individuals. However, research evaluating the denture-associated microbiome in patients with an active pneumonia diagnosis is lacking. This research had two primary aims. Firstly, unrestricted characterisation of denture-associated bacterial communities in pneumonia patients and long-term care home residents, through 16S rRNA gene metataxonomic sequencing. Secondly, development of a model denture acrylic-associated biofilm incorporating clinically relevant respiratory pathogens, to allow exploration of inter-microbial and host-microbial interactions in infection and testing of novel anti-biofilm strategies. There were significant shifts observed in species composition, diversity and richness in denture-associated microbiota of pneumonia patients. Importantly, the relative abundance of putative respiratory pathogens was significantly increased in pneumonia patients compared with respiratorily healthy care home residents. The magnitude of this increase was approximately tripled in denture-associated bacterial communities compared with other oral sites examined. An in vitro denture-acrylic biofilm model was developed incorporating the respiratory pathogens Staphylococcus aureus and Pseudomonas aeruginosa. This model was extensively characterised using a range of techniques and showed excellent scalability to high throughput applications. Subsequent infection of epithelial tissue models revealed the role of P. aeruginosa in instigating tissue invasion and disruption. A potential novel function for the pseudomonal aprA gene, encoding alkaline protease was suggested; providing a competitive advantage to this microorganism in mixed-species infections. A range of novel antimicrobial compounds was screened for biocidal activity and successfully incorporated into silicone biomaterials. However, antimicrobial activity of several tested compounds was abated in biomaterials. Highly controlled microwave energy delivery using a cavity resonator showed considerable promise as a denture sterilisation modality. This work was novel in several aspects. The in vitro model was the first model of denture-associated biofilms to incorporate respiratory pathogens, and subsequent molecular characterisation revealed the biogeography of microorganisms within the biofilm and in tissue infections. The models were subsequently employed in a high throughput screening assay wherein novel antimicrobial compounds and antibiofilm methods were tested. The clinical study was the first to examine the dentureassociated oral microbiome in pneumonia patients, with novel insights into changes in bacterial composition associated with respiratory infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science (General)