Functional Analysis of a Putative Group A Streptococcal 5’ Nucleotidase

Abstract

Streptococcus pyogenes is a major Gram-positive, human pathogen. It employs a wide array of virulence factors to cause disease but many of these factors have yet to be elucidated. This project aimed to further characterise the function of one such protein, the putative cell wall anchored Streptococcal 5’ nucleotidase (S5nA). Through the production of a recombinant version of the protein, the properties of S5nA were investigated using a number of biochemical and functional assays. S5nA was found to be immune protective in whole blood killing assays, indicating a function for this protein in S. pyogenes immune evasion. S5nA was also found to be able to produce the cytotoxic compounds adenosine and deoxyadenosine through its enzymatic activity and cause the death of THP-1 monocytes. The enzymatic function of S5nA was discovered to be synergistically enhanced by the DNase activity of another streptococcal cell wall anchored protein.