The Role of Hfq in S. aureus Gene Regulation

Staphylococcus aureus is an important opportunistic pathogen, capable of causing a wide range of diseases. This ability to colonise and infect a variety of different tissues is due to the number of virulence factors it can produce. These factors are tightly regulated so they are only expressed when required and allow rapid adaptation to changing environments. In other bacteria the RNA binding protein Hfq is important for growth, resistance to stresses and virulence. Hfq regulation occurs through RNA stability, processing and translation. However the role of Hfq in S. aureus is controversial as conflicting reports on the subject have been published. Preliminary work in our laboratory indicated a role for Hfq in the positive regulation by the DNA binding protein Fur but the mechanisms involved are unknown. Therefore the aim of this study is to identify targets for Hfq regulation and investigate how Fur is involved in this regulation. This work demonstrates that S. aureus Hfq, along with Fur, has a key role in the resistance to oxidative stress and the regulation of several important virulence genes including the immune evasion factor, Eap. Hfq was found to regulate eap expression at the post transcriptional level. In addition, both Hfq and Fur were found to regulate eap expression transcriptionally, possibly through regulation of sae, an important virulence gene regulator. Fe-Fur was shown to directly bind the sae promoters suggesting direct positive regulation of sae by Fur. But the mechanisms involved in Hfq regulation remain unclear as Hfq did not have a major affect eap or sae mRNA stability. The regulation by Hfq and Fur shows some strain variation indicating that other factors are involved. Therefore Hfq and Fur play key roles in S. aureus virulence regulation. Further understanding of this complex regulatory network may reveal new targets for antimicrobial development to combat this important pathogen.