During analysis of Legionella pneumophila genome sequence, the team from the Biology of Intracellular Bacteria Unit (Institut Pasteur/CNRS), headed by Carmen Buchrieser, identified genes coding for proteins that were predicted to be involved in the infection of human cells. In this study, published in the journal PNAS, the researchers show that one of these proteins is secreted in the human cell and helps to block the antibacterial response of the infected cells.
In 2014 over 1,300 people in France contracted legionelloses and nearly 130 died. Recently, this infectious disease has particularly hit the US where it was diagnosed in 87 patients in Flint (Michigan), and Portugal where over 300 people were infected, and seven died. This emerging disease is caused by Legionella pneumophila, an environmental bacterium that can grow in hot water systems. Legionella pneumophila is an intracellular bacterium that has a very sophisticated system to exploit the host cell functions to its own advantage. During analysis of its genome sequence, the team from the Biology of Intracellular Bacteria Unit (Institut Pasteur/CNRS), headed by Carmen Buchrieser, identified genes coding for proteins that were predicted to be involved in the infection of human cells. These proteins resemble proteins of higher organisms (eukaryotes), including humans, and can modify the physiology of the infected host cells. They are thus potential virulence factors. In this study, published in the journal PNAS, the researchers show that one of these proteins is secreted in the human cell and helps to block the antibacterial response of the infected cells.
The collaborative research of scientists belonging to different international teams has revealed that the bacterium Legionella pneumophila (a prokaryote) has acquired a eukaryotic gene that is coding for a major player in lipid metabolism in human cell membranes. For the first time, this research has shown that a change lipid metabolism in the host cell is triggered during bacterial infection. In particular, the researchers have identified and demonstrated the role of a key factor — a sphingosine-1-phosphate lyase (LpSpl) — produced by the bacterium that induces certain of these metabolic changes in the host cell. The researchers have solved the structure of this protein and have observed that it is perfectly conserved with its eukaryotic homolog. This suggests that one virulence strategy of Legionella pneumophila is to mimic the functions of human proteins.
To fully characterize the activity of this protein during infection, the researchers have studied its functional role and have discovered that it has a major effect on the autophagic response in the host cell, i.e. on the degradation of cellular proteins and invading pathogenic bacteria. By blocking the cellular defense mechanisms based on autophagy, the bacterium manages to avoid being degraded by the cell. This mechanism, which contributes to the development of legionellosis, has been confirmed in a mouse model of infection.
Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy, PNAS, February 1st, 2016.
Monica Rolandoa,b,1, Pedro Escolla,b,1, Tamara Noraa,b, Joëlle Bottic,d, Valérie Boitezc,d, Carmen Bediae,2, Craig Danielsf,3, Gilu Abrahamg, Peter J. Stogiosf, Tatiana Skarinaf, Charlotte Christophea,b, Delphine Dervins-Ravaulta,b, Christel Cazaleta,b, Hubert Hilbih, Thusitha W. T. Rupasinghei, Dedreia Tulli, Malcolm J. McConvillei,j, Sze Ying Ongk, Elizabeth L. Hartlandk, Patrice Codognoc,d, Thierry Levadee, Thomas Nadererg, Alexei Savchenkof, and Carmen Buchriesera,b
(a) Institut Pasteur, Biologie des Bactéries Intracellulaires, Paris, France
(b) CNRS UMR 3525, 75724 Paris, France
(c) Institut Necker Enfants-Malades, INSERM U1151-CNRS UMR 8253, France
(d) Université Paris Descartes-Sorbonne Paris Cité, Paris, France
(e) INSERM UMR1037, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France
(f) Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Canada
(g) Department of Biochemistry and Molecular Biology and the Biomedicine Discovery Institute, Monash University, VIC, Australia
(h) Institute of Medical Microbiology, University of Zürich, Switzerland
(i) Metabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC, Australia
(j) Department of Biochemistry and Molecular Biology, The University of Melbourne, VIC, Australia
(k) Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, VIC, Australia
(1) M.R. and P.E. contributed equally to this work.
(2) Present address: Institute of Environmental Assessment and Water Research (IDAEACSIC), Barcelona, Spain.
(3) Present address: Hospital for Sick Children, Toronto, Ontario, Canada.
Mis à jour le 03/02/2016