Shigella Spa47 Regulator Proteins Provide a Potential Means of Controlling Type Three Secretion System Activation and Pathogen Virulence

Shigella flexneri is a gram negative bacterial pathogen and is the causative agent of bacillary dysentery. Like many related pathogens, Shigella uses a type three secretion system (T3SS) to infect targeted host cells and avoid host immune responses. Within the T3SS, we have identified the protein Spa47 as an active ATPase that is essential for apparatus formation and the ability of Shigella to cause infection. Specifically, Spa47 knockout and or mutant strains of Shigella are non-virulent while complemented strains regain virulence, suggesting that control over of Spa47 activity may ultimately serve to regulate Shigella virulence in vivo. In this study, we identify and characterize Shigella proteins that interact with Spa47 and find that these interactions do in fact serve to regulate Spa47 activity in vitro, providing valuable insight into the mechanism of Shigella virulence regulation and providing a valuable target for much needed non-antibiotic based anti-infective treatments