Research Projects

Burkholderia species are associated with several life-threatening human infections that often result in high morbidity and mortality rates due to their innate resistance to antibiotics. To improve clinical outcomes new therapies are needed which target conserved, yet unique, Burkholderia pathways. One such pathway is the Burkholderia O-linked protein glycosylation system which is required for virulence in Burkholderia cenocepacia and Burkholderia pseudomallei. This system relies on the O-Glycosylation gene Cluster (ogc), a five gene cluster sufficient and required for the generation of the glycan used for protein glycosylation, and the distally encoded oligosaccharyltransferase, pglL, responsible for the ligation of glycans to glycoproteins. Previous research from the lab has shown that the disruption of genes within the ogc cluster or pglL leads to profound impacts on bacterial physiology suggesting the perturbation of glycosylation may provide a novel way to control infections. Thus, this work aims to understand the sensitivity of the Burkholderia O-linked glycosylation system to manipulation and how glycosylation impacts the viability of B. cenocepacia. Utilising system biology approaches such as proteomic and CRISPRi as well as phenotypic assessments including growth/stress assays this work will explore if the dysregulation of protein glycosylation could be used as a next generation therapy to control Burkholderia infections.

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