D-Arabinan hydrolysis and its roles in mycobacteriales biology

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Benedict, Samuel ORCID: https://orcid.org/0000-0002-8941-3703 (2024). D-Arabinan hydrolysis and its roles in mycobacteriales biology. University of Birmingham. Ph.D.

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Abstract

Microbial arabinogalactans are rare in nature, restricted to the order Mycobacteriales, where it plays a critical function covalently tethering the exterior mycomembrane to the inner peptidoglycan sacculus. To date, no enzyme or group of enzymes had been discovered which were capable of the breakdown of this complex polysaccharide. In work prior to this thesis, our group reported the first such group of enzymes in gut resident bacteria.

This thesis explores the functional diversity of two new enzyme families, GH183 and GH172 which are conserved across Mycobacteriales species. In the first chapter, endogenous homologs of the GH183 enzyme family in Mycobacterium tuberculosis and it's non pathogenic relative Mycobacterium smegmatis are characterised using biochemical and structural methodologies. In the second chapter, a GH172 enzyme is demonstrated to be involved in a putative recycling locus in the human pathogen Nocardia brasiliensis. Finally, in the third chapter, we explore homologs of the GH183 enzyme which appear to be involved in intraspecies competition. In summary, this thesis reports on the discovery of two new enzyme families and their roles in the homeostasis of the Mycobacteriales cell wall, with significant implications across mycobacteriology, including in treatment of high priority mycobacterial disease such as tuberculosis.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):