Engineering enzymes to probe novel antibiotic targets within sialic acid catabolism — ASN Events

Engineering enzymes to probe novel antibiotic targets within sialic acid catabolism (#378)

Rachel A North 1 , Sarah A Kessans 1 , Renwick C J Dobson 1 2
  1. Biomolecular Interaction Centre, University of Canterbury, Christchurch, New Zealand
  2. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia

Sialic acids are undoubtedly one of the most important carbohydrate classes in biology. Interestingly, several bacterial pathogens can scavenge sialic acid from their surrounding environment and degrade it as a source of carbon, nitrogen and energy. This sequestration and subsequent catabolism of sialic acid requires a cluster of genes known as the ‘Nan-Nag’ cluster. This pathway has been well documented in several bacterial pathogens that colonise mucous-rich niches, such as methicillin-resistant Staphylococcus aureus, suggesting that the ability to utilise sialic acid as a ubiquitous carbon and nitrogen source is important for colonisation and persistence. Importantly, the Nan-Nag genes have proven essential for Staphylococcus aureus growth on sialic acids, making the pathway a viable antimicrobial drug target. A biophysical and structural characterisation of the catabolic enzymes involved in the breakdown of sialic acid from methicillin-resistant Staphylococcus aureus will be presented. Understanding the structural nature of these enzymes will provide us with the preliminary information necessary for on-going antimicrobial development.