Cellular and molecular aspects of Legionella pneumophila transport to the endoplasmic reticulum.

摘要

Legionella pneumophila is a member of a class of bacterial pathogens that alter phagosome transport within eukaryotic cells. Phagosomes containing L. pneumophila evade transport to lysosomes, forming an endoplasmic reticulum-like organelle that supports bacterial replication. The L. pneumophila-encoded Dot/Icm secretion system injects virulence factors into host cells. These factors are proposed to play a role in altering phagosome transport, allowing for the establishment of a replicative organelle. In this study, the roles of several key regulators of vesicular transport within mammalian cells was examined to identify the host cellular pathways that are manipulated by the putative substrates of the Dot/Icm secretion system.; The fate of L. pneumophila within macrophages can be dictated by the activity of the endocytic pathway of the host. Overexpression of rab7, a GTPases that controls late endocytic transport, inhibited the efficiency that L. pneumophila formed replicative organelles. Interfering with the rab7 function promoted the establishment of a replicative organelle. However, disrupting transport to lysosomes is not the sole function of the Dot/Icm substrates. Inhibiting rab-mediated transport to lysosomes did not complement the intracellular growth defects of dot/icm mutants.; The ability of LCPs to intercept vesicles at endoplasmic reticulum exit sites correlated with the ability to form replicative organelles. Both events were dot/icm-dependant and required ARF1 and Sar1, host proteins that regulate vesicular transport in the early secretory pathway. Collectively, these data reveal that ARF-regulated vesicular transport in the early secretory pathway is exploited by L. pneumophila to maintain residence in a non-endocytic, replicative organelle.