Investigating a Sialic Acid Derivative import and utilisation pathway in a bacterial respiratory pathogen

The SARS-Cov-2 pandemic has claimed hundreds of thousands of lives to date and remains one of the unprecedented global health emergencies of this century. Amongst the public, it is generally unrecognised that 50% of the fatalities during the SARS-CoV-2 epidemic are caused by untreated or untreatable secondary bacterial infections, in most cases in the lung (Zhou et al., 2020). S. pneumoniae,  H. influenzae, are amongst some of the most commonly isolated bacteria during secondary infections. Our laboratory studies metabolite uptake systems in these bacteria with the aim of providing structural and biochemical data for antimicrobial development and treatment regimens that are still sorely needed in the light of the SARS-Cov-2 pandemic. 

Sialic acid (SIA) is vital energy source for a host of lung bacteria. S. pneumoniae possesses enzymes to convert SIA to a sialic acid derivative (SIA-D) to withdraw SIA from the nutrient pool and make it unavailable for competitor bacterial species. Our lab has recently uncovered the role of a S. pneumoniae protein in binding SIA-D allowing us to propose roles for the genes that are linked to this protein within the same bacterial operon. We hypothesise that the products of these genes are responsible for transporting the SIA-D across the membrane and for reactions that reinsert SIA-D into bacterial energy pathways. In our preliminary studies we have cloned and tested these genes for soluble protein expression with positive results. The project is therefore ideal for a Year-In-Industry student with the strong prospect of generating quality protein samples that form the foundation of subsequent studies.  It is therefore expected that the student will get trained in X-ray crystallography, EM as well as biophysical methods (e.g. ITC, SPR). The desired outcome of the work will be to contribute to a team publication characterising the SIA-D import and processing pathway.