| Title: |
Sel1 Repeat Protein LpnE Is a Legionella pneumophilaVirulence Determinant That Influences Vacuolar Trafficking |
| Authors: |
Newton, Hayley J., Sansom, Fiona M., Dao, Jenny, McAlister, Adrian D., Sloan, Joan, Cianciotto, Nicholas P., Hartland, Elizabeth L. |
| Source: |
Infection and Immunity; December 2007, Vol. 75 Issue: 12 p5575-5585, 11p |
| Abstract: |
ABSTRACTThe environmental pathogen Legionella pneumophilapossesses five proteins with Sel1 repeats (SLRs) from the tetratricopeptide repeat protein family. Three of these proteins, LpnE, EnhC, and LidL, have been implicated in the ability of L. pneumophilato efficiently establish infection and/or manipulate host cell trafficking events. Previously, we showed that LpnE is important for L. pneumophilaentry into macrophages and epithelial cells. In further virulence studies here, we show that LpnE is also required for efficient infection of Acanthamoeba castellaniiby L. pneumophilaand for replication of L. pneumophilain the lungs of A/J mice. In addition, we found that the role of LpnE in host cell invasion is dependent on the eight SLR regions of the protein. A truncated form of LpnE lacking the two C-terminal SLR domains was unable to complement the invasion defect of an lpnEmutant of L. pneumophila130b in both the A549 and THP-1 cell lines. The lpnEmutant displayed impaired avoidance of LAMP-1 association, suggesting that LpnE influenced trafficking of the L. pneumophilavacuole, similar to the case for EnhC and LidL. We also found that LpnE was present in L. pneumophilaculture supernatants and that its export was independent of both the Lsp type II secretion system and the Dot/Icm type IV secretion system. The fact that LpnE was exported suggested that the protein may interact with a eukaryotic protein. Using LpnE as bait, we screened a HeLa cell cDNA library for interacting partners, using the yeast two-hybrid system. Examination of the protein-protein interaction between LpnE and a eukaryotic protein, obscurin-like protein 1, suggested that LpnE can interact with eukaryotic proteins containing immunoglobulin-like folds via the SLR regions. This investigation has further characterized the contribution of LpnE to L. pneumophilavirulence and, more specifically, the importance of the SLR regions to LpnE function. |
| Database: |
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