Characterisation of a membrane protein, MspA, that is critical for Staphylococcus aureus pathogenesis

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Staphylococcus aureus is one of the most common human pathogenic bacteria. It can cause various infections, ranging from superficial skin infections to sepsis and other life-threatening diseases. Due to the rise of antibiotic resistance, this microorganism has become a challenge to treat. To prevent disease and develop effective treatments, we need to understand the mechanisms used by this organism to cause disease. One approach undertaken to address this in Prof. Massey's lab is to apply a functional genomics approach, which has identified a novel membrane-bound protein gene called mspA (membrane stabilizing protein A). When the encoded protein is absent, the bacteria were found to lose their ability to produce cytolytic toxins, produce staphyloxanthin, and they became unable to control their iron homeostasis or adapt to iron-rich media, and they increased their resistance to β-lactam antibiotics and increased the amount of penicillin binding proteins PBPs in the cell membrane. Using a site-directed mutagenesis approach domains and amino acids within MspA that are critical to its activity have been identified. While work is still underway to understand how this protein exerts its pleiotropic effects on S. aureus, this work has characterised these effects and identified potential targets within this protein that could be used to develop a novel therapeutic approach to treat these bacteria in the future.
Date of Award21 Mar 2023
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorMatthew B Avison (Supervisor) & Ruth C Massey (Supervisor)

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