Streptococcus pyogenes, the causative agent of group A streptococcal infections, is responsible for over 500,000 deaths a year globally. It is primarily a pathogen affecting young children, particularly in developing countries 1. Despite an extreme sensitivity to penicillin, a resurgence in group A streptococcal infections has been observed since the 1980s 2. The looming threat of penicillin resistance, coupled with the stagnation in antibiotic development, demands that new targets for drug development be sought. One potential avenue for combating S.pyogenes infections is to pursue processes by which metal homeostasis is maintained within the cell 3.
While S.pyogenes has an essential requirement for zinc, an oversaturation of zinc within the cell is toxic 4. CzcD1 is a membrane protein that mediates zinc homeostasis in S.pyogenes by effluxing excess zinc from the cell. The inhibition or cessation of CzcD1 activity would potentially assist the infected host’s innate immune system in utilising zinc toxicity as a defence against infection. In this manner, the interruption of metal homeostasis would allow for the battle against group A streptococcal infections to be waged on a new front.
The main aim of my honours year project is to characterise the function and structure of CzcD1 from S.pyogenes. Progress toward the overexpression, purification and crystallisation of CzcD1 will be described.