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Infect. Immun. doi:10.1128/IAI.00443-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Sel1 repeat protein LpnE is a Legionella pneumophila virulence determinant that influences vacuolar trafficking

Australian Bacterial Pathogenesis Program, Department of Microbiology, Monash University, Victoria 3800, Australia and Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA, Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia

^* To whom correspondence should be addressed. Email: hartland{at}unimelb.edu.au.

	Abstract

The environmental pathogen Legionella pneumophila possesses 5 proteins with Sel1 repeats (SLRs) from the tetratricopeptide repeat (TPR) protein family. Three of these proteins, LpnE, EnhC and LidL, have been implicated in the ability of L. pneumophila to efficiently establish infection and/or manipulate host cell trafficking events. Previously, we showed that LpnE is important for L. pneumophila entry into macrophages and epithelial cells. In further virulence studies here, we show that LpnE is also required for efficient infection of Acanthamoeba castellanii by L. pneumophila and for replication of L. pneumophila in the lungs of A/J mice. In addition, we found that the role of LpnE in host cell invasion is dependent on the 8 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 lpnE mutant of L. pneumophila 130b in both A549 and THP-1 cell lines. The lpnE mutant displayed impaired avoidance of LAMP-1 association suggesting that LpnE influenced trafficking of the L. pneumophila vacuole, similar to EnhC and LidL. We also found that LpnE was present in L. pneumophila culture supernatants and that this 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 using the yeast two-hybrid system for interacting partners. 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 characterised the contribution of LpnE to L. pneumophila virulence, and more specifically the importance of the SLR regions to LpnE function.

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