Subversion of Host Membrane Dynamics by the Legionella Dot/Icm Type IV Secretion System

  • Hubert HilbiEmail author
  • Hiroki NagaiEmail author
  • Tomoko KuboriEmail author
  • Craig R. RoyEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 413)


Legionella species are Gram-negative ubiquitous environmental bacteria, which thrive in biofilms and parasitize protozoa. Employing an evolutionarily conserved mechanism, the opportunistic pathogens also replicate intracellularly in mammalian macrophages. This feature is a prerequisite for the pathogenicity of Legionella pneumophila, which causes the vast majority of clinical cases of a severe pneumonia, termed “Legionnaires’ disease.” In macrophages as well as in amoeba, L. pneumophila grows in a distinct membrane-bound compartment, the Legionella-containing vacuole (LCV). Formation of this replication-permissive pathogen compartment requires the bacterial Dot/Icm type IV secretion system (T4SS). Through the T4SS as many as 300 different “effector” proteins are injected into host cells, where they presumably subvert pivotal processes. Less than 40 Dot/Icm substrates have been characterized in detail to date, a number of which show unprecedented biological activities. Some of these effector proteins target host cell small GTPases, phosphoinositide lipids, the chelator phytate, the ubiquitination machinery, the retromer complex, the actin cytoskeleton, or the autophagy pathway. A recently discovered class of L. pneumophila effectors modulates the activity of other effectors and is termed “metaeffectors.” Here, we summarize recent insight into the cellular functions and biochemical activities of L. pneumophila effectors and metaeffectors targeting the host’s endocytic, retrograde, or autophagic pathways.


Amoebae Autophagy Dictyostelium Effector protein Endosome’ GTPase Host–pathogen interaction Intracellular bacteria Legionella Macrophage Pathogen vacuole Phosphoinositide lipid Retrograde transport Type IV secretion Vesicle trafficking 



Research in the laboratory of H. H. was supported by the Swiss National Science Foundation (SNF; 31003A_153200), the German Ministry of Education and Research (BMBF) in the context of the EU Infect-ERA initiative (project EUGENPATH), the Novartis Foundation for Medical-Biological Research, and the OPO foundation. Research in the laboratory of H. N. was supported in part by MEXT/JSPS KAKENHI Grants 15H01322, 15H04728, 16H05189, and 16K14724. Research in the laboratory of C. R. R. was funded by NIH grant R37 AI041699.


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institute of Medical Microbiology, University of ZürichZurichSwitzerland
  2. 2.School of MedicineGifu UniversityGifuJapan
  3. 3.Department of Microbial PathogenesisYale UniversityNew HavenUSA

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