The Legionella Effector RidL Inhibits Retrograde Trafficking to Promote Intracellular Replication

Ivo Finsel, Curdin Ragaz, Christine Hoffmann, Christopher F. Harrison, Stephen Weber, Vanessa A. van Rahden, Ludger Johannes, and Hubert Hilbi. Cell Host & Microbe. (2013) 14, 38–50

Speaker: Tao-Sheng Liu (劉道生)                                Time: 14:00~15:00, Mar. 24, 2014

Commentator: Dr. Lien-I Hor (何漣漪老師)               Place: Room 601

Abstract:

Legionella pneumophila is a kind of Gram negative bacteria causing Pontiac fever or Legionnaires’ disease, which can survive in free-living amoeba and macrophages, replicate intracellularlywith unique Legionella-containing vacuoles (LCVs)¹. The formation of LCVs belongs to type IV secretion system (T4SS)², which translocates effector proteins into host cells. In some cases, some bacterial toxins and some viruses might hijack the retrograde pathway to access the host cell.³ In this study, the authors showed Legionella pneumophila Icm/Dot substrate RidL binds the retromercargo recognition complex, inhibits retrograde trafficking and promotes intracellular bacterial replication. At first, the authors revealed T4SS effector RidL is located in LCVs, which not only support the growth of intracellular bacteria but also alter retrograde vesicle trafficking－the process of selected proteins transporting from endosomes to the Golgi complex. The authors proved theretromer complex which mediates retrograde trafficking located in LCVs independently with RidL. They not only proved the association between RidL and Vps29 through GST pull down assay but also founded the binding between RidL and the phospholipid PtdIns(3)P, which localizes retromer components to membranes. Sorting nexins can mediate protein capture and membraneremodeling, depleting RidL result in sorting nexins accumulation in LCVs. Etopic produced RifL inhibits retrograde trafficking. Furthermore, the authors found Legionella pneumophila inhibits retrograde trafficking at endosome exit sites in a RidL-dependent manner. Base on above findings, the authors have indentified RidL as a retromer inhibitior to promote intracellular bacterial replication.

References:

1.     Hilbi, H. et al. (2012). Secretive bacterial pathogens and the secretory pathway. Traffic 13, 1187–1197.

2.     Hubber, A. et al. (2010). Modulation of host cell function by Legionella pneumophila type IV effectors. Annu. Rev. Cell Dev. Biol. 26, 261–283.

3.     Bujny, M.V. et al. (2008). Sorting nexin-1 defines an early phase of Salmonella-containing vacuole-remodeling during Salmonella infection. J. Cell Sci. 121, 2027–2036