Although Salmonella are long-known pathogens, the precise mechanisms they use to infect are incompletely understood. The bacteria inject a protein cocktail into host cells using a molecular syringe, leading to dramatic rearrangements of cytoskeletal filaments below the cell membrane.
As a result, membrane waves called ruffles are formed, which enclose the bacteria, and apparently facilitate their invasion. The process is known as "ruffling," and, until now, researchers regarded the formation of these ruffles as absolutely essential for bacterial entry.
"We showed for the first time that membrane ruffles are not essential for the bacteria to penetrate the host cell membrane. Since ruffling was used so far as signature of successful host cell invasion by this pathogen, the usefulness of such methods has to be reconsidered," said Jan Hänisch, who performed most experiments in the course of his PhD-thesis. Cells that were engineered to lack those membrane ruffles normally induced during Salmonella infection still engulfed the bacteria.
The researchers also discovered a new piece in the puzzle of Salmonella entry, called WASH. This novel factor promotes bacterial invasion by contributing to the formation of host cell cytoskeletal filaments important for entry.
"Our results have significant impact on the molecular and mechanistic understanding of the infection strategy used by this pathogen, and on the development of novel strategies to screen for potential inhibitors of the entry process in the future," said co-author Klemens Rottner.
Citation: Jan Hänisch, Julia Ehinger, Markus Ladwein, Manfred Rohde, Emmanuel Derivery, Tanja Bosse, Anika Steffen, Dirk Bumann, Benjamin Misselwitz, Wolf-Dietrich Hardt, Alexis Gautreau, Theresia E. B. Stradal Klemens Rottner, 'Molecular dissection of Salmonella-induced membrane ruffling versus invasion', Cellular Microbiology online, October 2009; doi: 10.1111/j.1462-5822.2009.01380.x