Many species of bacteria swim using flagella, which consist of thin helical filaments turned by rotary motors in the cell membrane. Assembly of the bacterial flagellum depends on a specialized secretion apparatus at the base that exports the protein subunits needed to form exterior structures. The flagellar secretion apparatus obtains energy from the membrane ion gradient, and transports protein subunits more rapidly than other known export systems. At the center of the apparatus is a complex formed by the membrane proteins FliP, FIiQ, FIiR, FlhA, and FlhB. The mechanism of flagellar secretion is poorly understood, mainly due to the lack of information on this membrane-protein complex. The proposed work will use a variety of genetic and biochemical approaches to determine which proteins are essential for export, to elucidate their membrane topologies, and to identify functionally important domains and residues.
Many species of bacteria utilize an export apparatus termed the injectisome to introduce effector molecules into host cells in order to subvert host-cell defenses and enable infection, The flagellar secretion apparatus studied here is closely related to the injectisome. The major membrane-protein components in both systems are highly homologous, and mechanistic insights gleaned from the flagellar system will be applicable to the injectisome. Further, flagellar motility is a factor contributing to the virulence of a number of pathogenic species, The study of flagellar export will thus enhance our understanding of bacterial pathogenesis and may contribute to the development of new strategies for combating infection.
| Ward, Elizabeth; Renault, Thibaud T; Kim, Eun A et al. (2018) Type-III secretion pore formed by flagellar protein FliP. Mol Microbiol 107:94-103 |
| Erhardt, Marc; Wheatley, Paige; Kim, Eun A et al. (2017) Mechanism of type-III protein secretion: Regulation of FlhA conformation by a functionally critical charged-residue cluster. Mol Microbiol 104:234-249 |
