Gene regulation by alpha-hydroxyketone-mediated signaling in Legionella pneumophila

• Applicant: Professor Dr. Hubert Hilbi
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2011 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195621792

• Final Report Year: 2015

Final Report Abstract

Legionella pneumophila, the causative agent of Legionnaires´ pneumonia, employs for cellcell communication the small signaling molecule LAI-1 (3-hydroxypentadecane-4-one), which is produced and detected by the Lqs (Legionella quorum sensing) system. The system comprises the autoinducer synthase LqsA, the homologous sensor kinases LqsS and LqsT, and the prototypic response regulator LqsR . Genetic, biochemical and cell biological approaches indicated that Lqs-regulated processes include pathogen-phagocyte interactions, production of extracellular filaments and biofilms, as well as natural competence for DNA uptake. We identified and characterized (1) the novel L. pneumophila sensor kinase LqsT, (2) phosphorylation signaling through LqsS and LqsT onto LqsR, (3) inter-kingdom signaling of LAI-1 through the eukaryotic components IQGAP1, Cdc42 and ARHGEF9, as well as (4) regulation of LqsS- and LqsT-dependent phosphorylation signaling and gene expression by LAI-1. The original aims (ii) function and structure of the response regulator LqsR, and (iii) endogenous production of LAI-1 by L. pneumophila are the focus of ongoing studies.

Publications

• (2012) α-Hydroxyketone production and sensing by Legionella and Vibrio. Sensors 12: 2899-2919
  Tiaden, A. & Hilbi, H.
  
• (2013) Analysis of Legionella infection by flow cytometry. In Meth. Mol. Biol. 954, Legionella: methods and protocols. Buchrieser, C. & Hilbi, H. (eds.), Springer Press; pp. 233-249
  Tiaden, A., Kessler, A. & Hilbi, H.
  
• (2013) Legionella: a versatile model to study host pathogen interactions. In Meth. Mol. Biol. 954, Legionella: methods and protocols. Buchrieser, C. & Hilbi, H. (eds.), Springer Press; editorial, pp. v-xix
  Hilbi, H. & Buchrieser, C.
  
• (2013) The Legionella pneumophila orphan sensor kinase LqsT regulates competence and pathogen-host interactions as a component of the LAI-1 circuit. Environ. Microbiol. 15: 646-662
  Kessler, A., Schell, U., Sahr, T., Tiaden, A., Harrison, C. F., Buchrieser, C. & Hilbi, H.
  
• (2014) Phosphorylation signaling through the Legionella quorum sensing histidine kinases LqsS and LqsT converges on the response regulator LqsR. Mol. Microbiol. 92: 1039–1055
  Schell, U., Kessler, A. & Hilbi, H.
  
• (2014) The natural alternative: protozoa as cellular models for Legionella infection. Cell. Microbiol. 16: 15-26
  Hoffmann, C., Harrison, C. F. & Hilbi, H.