Exploring the pathways underlying the growth of Staphylococcus aureus in acidic stress conditions.
File(s)
Author(s)
Beetham, Catrin
Type
Thesis
Abstract
Staphylococcus aureus is an opportunistic pathogen capable of causing a range of human infections. During infection S. aureus encounters several hostile environments, including an acidic environment which is found on the skin, within macrophages and in the vagina. However, little is known about how S. aureus detects and responds to low pH. In this thesis, I explore the genes and pathways utilised by S. aureus to grow under acidic stress conditions. Previous work has shown that the signalling nucleotide c-di-AMP affects the ability of S. aureus to grow at low pH. Here I show that this does not occur due to a dysregulation of the urease enzyme and production of ammonia from urea. Secondly, I utilised a Transposon sequencing approach to identify genes which are either essential or detrimental for the fitness of S. aureus under acidic stress conditions. I identified 31 genes which are essential for the fitness of S. aureus at low pH, and subsequent follow up experiments revealed that individual inactivation of most of these genes conferred a growth defect at low pH. Finally, the Tn-Seq approach identified several novel genes and pathways which have previously not been associated with the acidic stress response of S. aureus. One such gene was 0846, which I show is a previously uncharacterised histidine transporter. Further experiments determined that histidine and its uptake via 0846 is essential for the growth of S. aureus at low pH, which I hypothesise to be because it eliminates the need for the bacteria to synthesise histidine which
may be detrimental for growth under acid stress conditions. Taken together, the data presented in this thesis expands our knowledge of the acidic stress response of S. aureus.
may be detrimental for growth under acid stress conditions. Taken together, the data presented in this thesis expands our knowledge of the acidic stress response of S. aureus.
Version
Open Access
Date Issued
2023-12-11
Date Awarded
01/07/2024
License URL
Advisor
Gründling, Angelika
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)