Molecular and biochemical characterisation of glycosyltransferases involved in cell wall assembly of Corynebacterineae

Jankute, Monika (2015). Molecular and biochemical characterisation of glycosyltransferases involved in cell wall assembly of Corynebacterineae. University of Birmingham. Ph.D.

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Abstract

\(Mycobacterium\) \(tuberculosis\), the etiological agent of tuberculosis, remains the leading cause of mortality from a single infectious organism. The persistence of this human pathogen is associated with its distinctive lipid rich cell wall structure that is highly impermeable to hydrophilic drugs. This highly complex and unique structure is crucial for the growth, viability and virulence of \(M.\) \(tuberculosis\), thus representing an attractive target for vaccine and drug development. In this study, we have demonstrated that enzymes involved in \(Corynebacterium\) \(glutamicum\) cell wall assembly and precursor formation build complicated multi-protein complexes. Specifically, we have identified 24 putative interactions \(in\) \(vivo\) between 12 proteins responsible for AG biosynthesis. Additionally, we have investigated enzymes involved in the assembly of both AG and LAM biosynthesis in \(M.\) \(smegmatis\) and \(C.\) \(glutamicum\). Finally, we examined biophysical characterisation of membrane cell wall proteins solubilised in a stryrene maleic acid polymer, demonstrating that detergent free extraction of highly hydrophobic proteins from corynebacteria is possible. These findings provide a useful recourse for understanding the biosynthesis and function of the vital cell wall (lipo)polysaccharides of \(Corynebacterineae\), as well as providing new therapeutic targets for drug design against the pathogenic species of \(M.\) \(tuberculosis\), \(Mycobacterium\) \(marinum\) and \(Corynebacterium\) \(diphtheriae\).

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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