Cell-envelope lipid remodelling in mycobacterium tuberculosis: the role of glycerophosphodiesterase 1 and the response to phosphate limitation
File(s)
Author(s)
Gray, Robert
Type
Thesis
Abstract
Mycobacterium tuberculosis is remarkable for the quantity and diversity of its envelope lipids. The composition of the envelope has been documented to alter in response to exogenous stresses and between bacterial growth versus stasis. Here, we expand upon the knowledge of lipid remodelling in Mtb through study first of a key enzyme involved in phospholipid degradation, glycerophosphodiesterase 1 (GlpQ1), and second, by charting the very extensive remodelling when Mtb is grown in zero phosphate conditions. In the latter, we unequivocally identify three classes of phosphorus-free lipids that substitute into the cell-envelope for phospholipids, two of which have seldom been studied in mycobacteria including one which has never before been directly demonstrated in Mtb. Additionally, we produce evidence for a fourth class of phosphorus-free, replacement lipid, which has never before been described in nature.
Finally, we propose a model for how GlpQ1-dependent and GlpQ1-independent lipid metabolism pathways may combine to allow Mtb to overcome phosphate limitation encountered inside the macrophage phagosome, important to establishing pulmonary infection in the host.
Finally, we propose a model for how GlpQ1-dependent and GlpQ1-independent lipid metabolism pathways may combine to allow Mtb to overcome phosphate limitation encountered inside the macrophage phagosome, important to establishing pulmonary infection in the host.
Version
Open Access
Date Issued
2023-04-26
Date Awarded
01/08/2023
License URL
Advisor
Tate, Edward
Sorio De Carvalho, Luiz
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)