Biosynthesis of the sheathed flagellum in Helicobacter pylori

Scott Edwards

 

Dr. Timothy Hoover

September 21 at 12:20pm in the Fralin Auditorium, Fralin Hall room 102

Hosted by X.J. Meng

 

I have been on the faculty in the Department of Microbiology at the University of Georgia (UGA) since 1991, and am currently Professor and Head of Microbiology. Prior to coming to UGA, I did post-doctoral studies under the direction of Dr. Sydney Kustu at the University of California at Berkeley.  My post-doctoral studies focused on molecular mechanisms of transcriptional activation of s54-dependent genes by bacterial enhancer-binding proteins.  My graduate studies were in the Biochemistry Department at the University of Wisconsin-Madison (Ph.D., 1988) under the direction of Dr. Paul Ludden.  The focus of my dissertation was the biosynthesis of the iron-molybdenum cofactor of nitrogenase.  For the past several years, the major emphasis of my laboratory has been to understand how bacteria coordinate gene expression with assembly of complex cellular structures.  Specifically, we have examined flagellar gene regulation in Helicobacter pylori and how it is coupled with assembly of the flagellum.  More recently, my lab has shifted its focus to study the mechanism of polar localization of flagella and the unknown process of flagellar sheath biogenesis in H. pylori.

Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach where it can cause a variety of diseases including chronic gastritis, peptic ulcer disease or gastric cancer. H. pylori cells use a cluster of polar, sheathed flagella to penetrate the gastric mucin layer and reach the epithelium for colonization.  The flagellar sheath is contiguous with the outer membrane, and is proposed to protect the flagellar filament from depolymerization by gastric acid and to promote adherence to the gastric epithelium. While these proposed functions suggest a critical role for the flagellar sheath in host colonization, mechanisms of sheath biosynthesis have yet to be identified for any bacterial species.  Recent data from my lab indicate that cardiolipin, an anionic glycerophospholipid, is required for flagellar biosynthesis in H. pylori.  We identified an efflux system that we hypothesize to transport cardiolipin across the cell envelope for incorporation into the flagellar sheath.  Cryo-electron tomography suggests the efflux system forms a cage-like structure that surrounds the flagellar motor.  Our studies have led to a new model for flagellar sheath biosynthesis in H. pylori that can serve as a paradigm for sheathed flagella of other bacterial species.

Tsang, J., Hirano, T., Hoover, T.R. & McMurry, J.L. (2015). Helicobacter pylori FlhA binds the sensor kinase and flagellar gene regulatory protein FlgS with high affinity. Journal of Bacteriology 197:1886-1892.

Qin, Z., Lin W.T., Zhu S., Franco A.T. & Liu J. (2017). Imaging the motility and chemotaxis machineries in Helicobacter pylori by cryo-electron tomography. Journal of Bacteriology 199:e00695-16.

Zhu, S., Nishikino T., Hu B., Kojima S., Homma M. & Liu J. (2017). Molecular architecture of the sheathed polar flagellum in Vibrio alginolyticus. Proceedings of the National Academy of Sciences USA 114:10966-10971.

Edwards Flyer

This seminar will be livestreamed and recorded on the Fralin YouTube channel.