Roles and Regulation of a Shigella protease, IcsP

Helen Wing, Ph.D. (University of Nevada, Las Vegas)

The emergence and spread of antibiotic resistance among bacterial species is rapidly becoming a global health problem. This phenomenon is becoming increasingly common among bacterial agents of diarrheal disease, which is the second biggest killer of children under the age of five in the developing world today (WHO). Shigella species are enteric pathogens that cause severe, bloody diarrhea that kills approx. 1.1 million people per year. An enhanced understanding of the molecular basis of the biology and pathogenicity of Shigella will be critical for the development of new prevention and intervention strategies.

> Proteins that lie on the bacterial cell surface play key roles in bacterial pathogens, primarily because they lie at the bacterial-host interface. To date it is unclear to what extent Shigella species modulate these important virulence proteins during infection. Research in the Wing lab primarily focuses on virulence genes and their expression in Shigella, many of which lie on a large 230kb virulence plasmid. The Nevada INBRE program supports our investigation of one of these genes, icsP, which encodes an outer membrane protease. Due to its location and based on preliminary proteomic analyses, we hypothesize that i) IcsP proteolytically cleaves other outer membrane proteins of Shigella and ii) this has important consequences for Shigella virulence. In a second avenue of investigation, we are fully characterizing the transcriptional regulation of the icsP gene (Castellanos et al., 2009; Hensley et al 2011). We anticipate that these studies will improve our understanding of mechanisms of virulence gene expression in Shigella and in other closely related bacterial pathogens that also cause diarrheal disease.