Investigating the metabolism of non-aureus staphylococci relevant to prosthetic joint infection

Diaz Calvo, Teresa (2020) Investigating the metabolism of non-aureus staphylococci relevant to prosthetic joint infection. Doctoral thesis, University of East Anglia.

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Prosthetic joint infection (PJI) is a complication of joint replacement that occurs when bacteria adhere to the surface of a prosthetic joint and form a biofilm (Becker et al. 2014; Tande et al. 2014). Treatment is expensive and aggressive, constituting a major burden to the healthcare system and to the patients (Becker et al. 2014; Tande et al. 2014). Non-aureus staphylococci account for approximately 30% of all cases (Becker et al. 2014), with S. epidermidis being the main species involved (Becker et al. 2014), showing an increasing pathogenic potential (Uribe-Alvarez et al. 2016). Despite this, little is known about the mechanism of infection, which is assumed to be biofilm formation. This work describes how the first highly curated genome-scale metabolic model for S. epidermidis RP62A was constructed, manually curated, validated against experimental data and analysed with linear-programming techniques to explore the metabolism of cells living in joints. We defined routes for production of energy, planktonic biomass and biofilm polymers during growth on nutrients found in synovial fluid and under the range of conditions encountered across the biofilm structure: the results obtained indicated that the metabolic network re-arranges itself, varying the uptake and metabolism of glucose and amino acids in response to environmental changes and highlighted the importance of the uptake and catabolism of citrulline for ATP production, a pathway that, to our knowledge, has not been described before in this context. This work also provided an explanation for experimental observations where a decrease in the production of biofilm was observed in vitro upon glutamate deprivation, linking its catabolism with the synthesis of ATP, and suggested that the cell’s ability to modify the level of de-acetylated residues in biofilm exopolysaccharides is an important feature of biofilm formation. Finally, it exemplified how metabolic modelling can be useful in anticipating regulatory patterns leading to optimal bacterial growth strategies in different environments. This work is being developed further with a focus on informing the pathogenesis of non-aureus staphylococci in PJI.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Chris White
Date Deposited: 01 Sep 2020 10:12
Last Modified: 01 Sep 2020 10:12


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