Characterizing the dual regulation ofNeisseria gonorrhoeae tdfJin response to zinc and iron

Abstract

ABSTRACTGonorrhea is a sexually transmitted infection, caused by the bacterial pathogenNeisseria gonorrhea(Ngo) and affects millions of individuals of all age groups across the globe every year. Infection withNgodoes not result in protection and no effective vaccine has been developed, leaving antibiotics as the only treatment option. With the emergence of strains showing high levels of antibiotic resistance, there is an urgent need for development of novel therapeutics for disease prevention. During pathogenesis the host employs nutritional immunity, to restrict important transition metals such as zinc away fromNgo. This process is counteracted inNgoby the production of highly efficient zinc import TonB-dependent Transporters (TDTs) which are promising vaccine antigens and zinc shuttle ABC transporters found to be important for intracellular survival. InNgozinc homeostasis and transport proteins are regulated by the Zinc uptake regulator (Zur) which represses transcription in the presence of zinc and activates transcription in the absence of zinc. In this study, characterize the promoter elements of the zinc import TDT,tdfJ, which results in dual regulation by zinc and iron. We characterize specificity and binding affinities for regulation oftdfJby a second regulator, Ferric uptake regulator (Fur) in response to iron. The response oftdfJto both iron and zinc and its potential to be an important invasin, makes it an attractive candidate to investigate female genital tract infections. The female genital tract is a conglomerate of these conditions and infections here are often asymptomatic. Taken together, this research provides important knowledge on the regulation of virulence mechanisms in response to zinc, which will aid in the development of therapeutics and an efficacious vaccine against a gonococcal infection.