A mycobacterial glycoside hydrolase 76 enzyme enables arabinomannan release to signal exit from lag phase

Franklin, Aaron (2024). A mycobacterial glycoside hydrolase 76 enzyme enables arabinomannan release to signal exit from lag phase. University of Birmingham. Ph.D.

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Abstract

A key component of the mycobacterial cell envelope are the glycolipids. These molecules play important roles in both structural support and modulation of the host immune system. One of the major phospholipids produced by mycobacteria is phosphatidylinositol. This molecule can be glycosylated to produce phosphatidylinositol mannosides, as well as lipomannan and lipoarabinomannan. These mannosylated glycolipids make up the majority of the lipids in the cytoplasmic membrane. However, within the capsule of mycobacteria are lipid-free glycans thought to be derived from lipomannan and lipoarabinomannan. Currently, there is no explanation as to how arabinomannan and mannan are released from their lipid anchors. In this thesis, a glycoside hydrolase family 76 enzyme is identified which cleaves lipomannan and lipoarabinomannan and drives export of the carbohydrate domains to the capsule. In addition, this thesis demonstrates that the loss of this enzymes activity results in a loss of capsular arabinomannan. Furthermore, the loss of arabinomannan leads to an increase in lag phase and significantly slower exponential growth. This thesis provides evidence that arabinomannan acts as a signalling molecule which triggers the transition from lag phase to exponential growth. The findings presented in this thesis will serve as a basis for a better understanding of the digestion of mycobacterial glycolipids and the trafficking of these molecules to the outer most layer of the cell. This may lead to a more detailed appreciation of the role lipoarabinomannan and its derivatives play in host- pathogen interactions and bacterial physiology.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):