Gonorrhoea is a sexually transmissible infection caused by the bacterium Neisseria gonorrhoea. This infection is of major health concern due to high rates of disease, and rapidly diminishing treatment options due to drug resistance. Ceftriaxone is the current first line treatment in most countries and there is no identified ideal alternative. The emergence of multiple drug resistant (MDR) strains with elevated minimal inhibitory concentration values to ceftriaxone have been reported in many countries including Australia. Reports of MDR strains of N. gonorrhoeae resistant to ceftriaxone - termed extensively drug resistant (XDR), have caused considerable alarm [1-5]; The World Health Organisation has issued a Global Action Plan to minimise the spread and impact of antimicrobial resistance in N. gonorrhoeae, calling for the development of new treatments as an urgent priority. In 2013 the USA Centres for Disease Control and Prevention identified N. gonorrhoeae drug resistance in the top 3 of antibiotic resistance threats. With no ideal alternative treatment or vaccine available, it is widely feared that gonorrhoea will become untreatable, thus there is an urgent need for development of new antimicrobials.

The fatty acid synthesis type II (FASII) enzymes of N. gonorrhoeae, responsible for lipid biogenesis, represent an attractive target for the discovery of new antimicrobials (reviewed in [6]). Significantly, FabG and FabI, the two reductase enzymes of the FASII pathway, are inhibited by epigallocatechin gallate (EGCG) [7-8]. We have recently determined the structures of the FASII reductases FabG and FabI, and that of FabI in complex with EGCG, NADH, and NAD:triclosan, providing detailed knowledge of the active and cofactor binding sites within both enzymes. The binding sites for EGCG and NADH in FabI are highly similar in FabG providing a basis for design of inhibitors that simultaneously target both enzymes and a strong platform towards the development of urgently needed antimicrobials.