Investigation of the Role of Lytic Transglycosylases in Growth, Virulence, Persistence and Resuscitation of Burkholderia pseudomallei

Peptidoglycan is an essential component of bacterial cells. It is synthesised and remodelled by complex machinery consisting of multiple enzymes, including lytic transglycosylases (LTG’s). LTG’s are secreted and cell wall bound enzymes that play diverse roles in peptidoglycan remodelling, antimicrobial resistance and insertion of important structures such secretion systems. In mycobacteria LTG’s are called Resuscitation-promoting factors (Rpf’s) and are essential for the resuscitation of dormant cells and reactivation of latent infection.

Burkholderia pseudomallei is a Gram-negative non-spore-forming bacterium, the causative agent of melioidosis. It has at least 5 LTG’s and we hypothesise that similarly to Rpf’s in mycobacteria, they are important for virulence, persistence and reactivation of dormant B. pseudomallei. Recently we have generated a panel of LTG deletion mutants and demonstrated that these enzymes are important for division, motility and antimicrobial resistance in B. pseudomallei.

The current project aims to further investigate the role the LTG’s play in chronic and active infection, dormancy and resuscitation as well as understanding other molecular mechanisms involved. Experimental approaches will include infection experiments, expression and purification of recombinant LTG, peptidoglycan analysis, pull-down and mass-spectrometry immunoassays.

We seek for a highly motivated student with a strong interest in molecular microbiology and bacterial physiology. The student will be supervised by a scientific supervisory team with extensive experience in bacterial physiology, molecular biology, host-pathogen interactions and biochemistry.