J. P. Bardill, J. L. Miller, and J. P. Vogel, IcmS-dependent translocation of SdeA into macrophages by the Legionella pneumophila type IV secretion system, Mol Microbiol, vol.56, issue.1, pp.90-103, 2005.

R. M. Barrozo, Functional plasticity in the type IV secretion system of Helicobacter pylori, PLoS Pathog, vol.9, issue.2, p.1003189, 2013.

K. H. Berger, J. J. Merriam, and R. R. Isberg, Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene, Mol Microbiol, vol.14, issue.4, pp.809-822, 1994.

D. K. Boamah, G. Zhou, A. W. Ensminger, and T. J. O'connor, From many hosts, one accidental pathogen: the diverse protozoan hosts of Legionella, Front Cell Infect Microbiol, vol.7, p.477, 2017.

D. Burstein, Genome-scale identification of Legionella pneumophila effectors using a machine learning approach, PLoS Pathog, vol.5, issue.7, p.1000508, 2009.

D. Burstein, Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires, Nat Genet, vol.48, issue.2, pp.167-175, 2016.

B. A. Buscher, The DotL protein, a member of the TraG-coupling protein family, is essential for viability of Legionella pneumophila strain Lp02, J Bacteriol, vol.187, issue.9, pp.2927-2938, 2005.

J. Castresana, Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis, Mol Biol Evol, vol.17, issue.4, pp.540-552, 2000.

D. Chetrit, B. Hu, P. J. Christie, C. R. Roy, and J. Liu, A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel, Nat Microbiol, vol.3, issue.6, pp.678-686, 2018.

P. J. Christie, G. Valero, L. Buchrieser, and C. , Biological diversity and evolution of type IV secretion systems, Curr Top Microbiol Immunol, vol.413, pp.1-30, 2017.
URL : https://hal.archives-ouvertes.fr/pasteur-02168291

P. J. Christie and J. P. Vogel, Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells, Trends Microbiol, vol.8, issue.8, pp.354-360, 2000.

J. Coers, Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth, Mol Microbiol, vol.38, issue.4, pp.719-736, 2000.

J. Costa, I. Tiago, D. Costa, M. S. Verissimo, and A. , Molecular evolution of Legionella pneumophila dotA gene, the contribution of natural environmental strains, Environ Microbiol, vol.12, issue.10, pp.2711-2729, 2010.

G. Dumenil and R. R. Isberg, The Legionella pneumophila IcmR protein exhibits chaperone activity for IcmQ by preventing its participation in high-molecular-weight complexes, Mol Microbiol, vol.40, issue.5, pp.1113-1127, 2001.

G. Dumenil, T. P. Montminy, M. Tang, and R. R. Isberg, IcmR-regulated membrane insertion and efflux by the Legionella pneumophila IcmQ protein, J Biol Chem, vol.279, pp.4686-4695, 2004.

P. H. Edelstein, M. A. Edelstein, F. Higa, and S. Falkow, Discovery of virulence genes of Legionella pneumophila by using signature tagged mutagenesis in a guinea pig pneumonia model, Proc Natl Acad Sci U S A, vol.96, issue.14, pp.8190-8195, 1999.

P. H. Edelstein, B. Hu, F. Higa, and M. A. Edelstein, lvgA, a novel Legionella pneumophila virulence factor, Infect Immun, vol.71, issue.5, pp.2394-2403, 2003.

A. W. Ensminger, Legionella pneumophila, armed to the hilt: justifying the largest arsenal of effectors in the bacterial world, Curr Opin Microbiol, vol.29, pp.74-80, 2016.

P. Escoll, S. Mondino, M. Rolando, and C. Buchrieser, Targeting of host organelles by pathogenic bacteria: a sophisticated subversion strategy, Nat Rev Microbiol, vol.14, issue.1, pp.5-19, 2016.
URL : https://hal.archives-ouvertes.fr/pasteur-01326394

J. D. Farelli, IcmQ in the Type 4b secretion system contains an NADþ binding domain, Structure, vol.21, issue.8, pp.1361-1373, 2013.

M. Feldman, T. Zusman, S. Hagag, and G. Segal, Coevolution between nonhomologous but functionally similar proteins and their conserved partners in the Legionella pathogenesis system, Proc Natl Acad Sci U S A, vol.102, issue.34, pp.12206-12211, 2005.

R. D. Finn, The Pfam protein families database: towards a more sustainable future, Nucleic Acids Res, vol.44, issue.D1, pp.279-285, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01294685

I. Finsel and H. Hilbi, Formation of a pathogen vacuole according to Legionella pneumophila: how to kill one bird with many stones, Cell Microbiol, vol.17, issue.7, pp.935-950, 2015.

M. Garcia-boronat, C. M. Diez-rivero, E. L. Reinherz, and P. A. Reche, PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery, Nucleic Acids Res, vol.36, pp.35-41, 2008.

D. Ghosal, Y. W. Chang, K. C. Jeong, J. P. Vogel, and G. J. Jensen, In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography, EMBO Rep, vol.18, issue.5, pp.726-732, 2017.

G. Valero, L. Runsiok, C. Cazalet, C. Buchrieser, and C. , Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions, Front Microbiol, vol.2, p.208, 2011.
URL : https://hal.archives-ouvertes.fr/pasteur-01422820

L. Gomez-valero, More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells, Proc Natl Acad Sci, vol.116, issue.6, pp.2265-2273, 2019.

L. Gomez-valero, Comparative analyses of Legionella species identifies genetic features of strains causing Legionnaires' disease, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01329875

, Genome Biol, vol.15, issue.11, p.505

F. X. Gomis-ruth, M. Sola, F. De-la-cruz, and M. Coll, Coupling factors in macromolecular type-IV secretion machineries, Curr Pharm Des, vol.10, issue.13, pp.1551-1565, 2004.

J. Guglielmini, F. De-la-cruz, and E. P. Rocha, Evolution of conjugation and type IV secretion systems, Mol Biol Evol, vol.30, issue.2, pp.315-331, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-01374951

D. S. Guttman, S. J. Gropp, R. L. Morgan, and P. W. Wang, Diversifying selection drives the evolution of the type III secretion system pilus of Pseudomonas syringae, Mol Biol Evol, vol.23, issue.12, pp.2342-2354, 2006.

R. S. Hegde and H. D. Bernstein, The surprising complexity of signal sequences, Trends Biochem Sci, vol.31, issue.10, pp.563-571, 2006.

L. Huang, The E Block motif is associated with Legionella pneumophila translocated substrates, Cell Microbiol, vol.13, issue.2, pp.227-245, 2011.

A. Hubber and C. R. Roy, Modulation of host cell function by Legionella pneumophila type IV effectors, Annu Rev Cell Dev Biol, vol.26, issue.1, pp.261-283, 2010.

R. R. Isberg, T. J. O'connor, and M. Heidtman, The Legionella pneumophila replication vacuole: making a cosy niche inside host cells, Nat Rev Microbiol, vol.7, issue.1, pp.13-24, 2009.

K. C. Jeong, D. Ghosal, Y. W. Chang, G. J. Jensen, and J. P. Vogel, Polar delivery of Legionella type IV secretion system substrates is essential for virulence, Proc Natl Acad Sci U S A, vol.114, issue.30, pp.8077-8082, 2017.

M. Kanehisa, Linking databases and organisms: genomeNet resources in Japan, Trends Biochem Sci, vol.22, issue.11, pp.442-444, 1997.

A. Khemiri, Outer-membrane proteomic maps and surfaceexposed proteins of Legionella pneumophila using cellular fractionation and fluorescent labelling, Anal Bioanal Chem, vol.390, issue.7, pp.1861-1871, 2008.
URL : https://hal.archives-ouvertes.fr/hal-02339158

K. S. Ko, S. K. Hong, H. K. Lee, M. Y. Park, and Y. H. Kook, Molecular evolution of the dotA gene in Legionella pneumophila, J Bacteriol, vol.185, issue.21, pp.6269-6277, 2003.

S. Kryazhimskiy and J. B. Plotkin, The population genetics of dN/dS, PLoS Genet, vol.4, issue.12, p.1000304, 2008.

T. Kubori, Native structure of a type IV secretion system core complex essential for Legionella pathogenesis, Proc Natl Acad Sci U S A, vol.111, issue.32, pp.11804-11809, 2014.

M. J. Kwak, Architecture of the type IV coupling protein complex of Legionella pneumophila, Nat Microbiol, vol.2, issue.9, p.17114, 2017.

H. M. Lam, O. Ratmann, and M. F. Boni, Improved algorithmic complexity for the 3SEQ recombination detection algorithm, Mol Biol Evol, vol.35, issue.1, pp.247-251, 2018.

I. Letunic and P. Bork, Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees, Nucleic Acids Res, vol.44, issue.W1, pp.242-245, 2016.

Z. Lifshitz, Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal, Proc Natl Acad Sci U S A, vol.110, issue.8, pp.707-715, 2013.

W. Liu, IBS: an illustrator for the presentation and visualization of biological sequences, Bioinformatics, vol.31, issue.20, pp.3359-3361, 2015.

A. Loytynoja, Phylogeny-aware alignment with PRANK, Methods Mol Biol, vol.1079, pp.155-170, 2014.

Z. Q. Luo and R. R. Isberg, Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer, Proc Natl Acad Sci U S A, vol.101, issue.3, pp.841-846, 2004.

D. P. Martin, P. Lemey, and D. Posada, Analysing recombination in nucleotide sequences, Mol Ecol Resour, vol.11, issue.6, pp.943-955, 2011.

M. Matthews and C. R. Roy, Identification and subcellular localization of the Legionella pneumophila IcmX protein: a factor essential for establishment of a replicative organelle in eukaryotic host cells, Infect Immun, vol.68, issue.7, pp.3971-3982, 2000.

A. Meir, D. Chetrit, L. Liu, C. R. Roy, and G. Waksman, Legionella DotM structure reveals a role in effector recruiting to the Type 4B secretion system, Nat Commun, vol.9, issue.1, p.507, 2018.

B. Murrell, Detecting individual sites subject to episodic diversifying selection, PLoS Genet, vol.8, issue.7, p.1002764, 2012.

B. Murrell, FUBAR: a fast, unconstrained Bayesian approximation for inferring selection, Mol Biol Evol, vol.30, issue.5, pp.1196-1205, 2013.

H. Nagai and T. Kubori, Type IVB secretion systems of Legionella and other Gram-negative bacteria, Front Microbiol, vol.2, p.136, 2011.

H. Nagai and C. R. Roy, The DotA protein from Legionella pneumophila is secreted by a novel process that requires the Dot/Icm transporter, EMBO J, vol.20, issue.21, pp.5962-5970, 2001.

N. Nakano, T. Kubori, M. Kinoshita, K. Imada, and H. Nagai, Crystal structure of Legionella DotD: insights into the relationship between type IVB and type II/III secretion systems, PLoS Pathog, vol.6, issue.10, p.1001129, 2010.

D. K. Ang, . Van-driel, . Ir, and E. L. Hartland, Evolutionary Dissection of the Dot/Icm System Based on Comparative Genomics of 58 Legionella Species Newton HJ, Clin Microbiol Rev, vol.23, issue.2, pp.274-298, 2010.

S. Ninio, D. M. Zuckman-cholon, E. D. Cambronne, and C. R. Roy, The Legionella IcmS-IcmW protein complex is important for Dot/Icmmediated protein translocation, Mol Microbiol, vol.55, issue.3, pp.912-926, 2005.

B. Nystedt, A. C. Frank, M. Thollesson, and S. G. Andersson, Diversifying selection and concerted evolution of a type IV secretion system in Bartonella, Mol Biol Evol, vol.25, issue.2, pp.287-300, 2008.

T. N. Petersen, S. Brunak, G. Von-heijne, and H. Nielsen, SignalP 4.0: discriminating signal peptides from transmembrane regions, Nat Methods, vol.8, issue.10, pp.785-786, 2011.

S. L. Pond, S. D. Frost, and S. V. Muse, HyPhy: hypothesis testing using phylogenies, Bioinformatics, vol.21, issue.5, pp.676-679, 2005.

J. Qiu and Z. Q. Luo, Legionella and Coxiella effectors: strength in diversity and activity, Nat Rev Microbiol, vol.15, issue.10, pp.591-605, 2017.

S. Raychaudhury, Structure and function of interacting IcmR-IcmQ domains from a type IVb secretion system in Legionella pneumophila, Structure, vol.17, issue.4, pp.590-601, 2009.

P. Rice, I. Longden, and A. Bleasby, EMBOSS: the European Molecular Biology Open Software Suite, Trends Genet, vol.16, issue.6, pp.276-277, 2000.

M. Rohde, J. Pü-ls, R. Buhrdorf, W. Fischer, and R. Haas, A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system, Mol Microbiol, vol.49, issue.1, pp.219-234, 2003.

C. R. Roy and R. R. Isberg, Topology of Legionella pneumophila DotA: an inner membrane protein required for replication in macrophages, Infect Immun, vol.65, issue.2, pp.571-578, 1997.

A. B. Sadosky, L. A. Wiater, and H. A. Shuman, Identification of Legionella pneumophila genes required for growth within and killing of human macrophages, Infect Immun, vol.61, issue.12, pp.5361-5373, 1993.

H. A. Schmidt, K. Strimmer, M. Vingron, V. Haeseler, and A. , TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing, Bioinformatics, vol.18, issue.3, pp.502-504, 2002.

G. Segal, M. Purcell, and H. A. Shuman, Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome, Proc Natl Acad Sci U S A, vol.95, issue.4, pp.1669-1674, 1998.

J. A. Sexton and J. S. Pinkner, The Legionella pneumophila PilT homologue DotB exhibits ATPase activity that is critical for intracellular growth, J Bacteriol, vol.186, issue.6, pp.1658-1666, 2004.

J. A. Sexton, J. L. Miller, A. Yoneda, T. E. Kehl-fie, and J. P. Vogel, Legionella pneumophila DotU and IcmF are required for stability of the Dot/Icm complex, Infect Immun, vol.72, issue.10, pp.5983-5992, 2004.

J. A. Sexton, H. J. Yeo, and J. P. Vogel, Genetic analysis of the Legionella pneumophila DotB ATPase reveals a role in type IV secretion system protein export, Mol Microbiol, vol.57, issue.1, pp.70-84, 2005.

H. Shimodaira and H. Hasegawa, Multiple comparisons of log-likelihoods with applications to phylogenetic inference, Mol Biol Evol, vol.16, issue.8, pp.1114-1116, 1999.

J. M. Smith, Analyzing the mosaic structure of genes, J Mol Evol, vol.34, issue.2, pp.126-129, 1992.

M. D. Smith, Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection, Mol Biol Evol, vol.32, issue.5, pp.1342-1353, 2015.

K. Strimmer, V. Haeseler, and A. , Likelihood-mapping: a simple method to visualize phylogenetic content of a sequence alignment, Proc Natl Acad Sci U S A, vol.94, issue.13, pp.6815-6819, 1997.

M. C. Sutherland, K. A. Binder, P. Y. Cualing, and J. P. Vogel, Reassessing the role of DotF in the Legionella pneumophila type IV secretion system, PLoS One, vol.8, issue.6, p.65529, 2013.

M. C. Sutherland, T. L. Nguyen, V. Tseng, and J. P. Vogel, The Legionella IcmSW complex directly interacts with DotL to mediate translocation of adaptor-dependent substrates, PLoS Pathog, vol.8, issue.9, p.1002910, 2012.

C. D. Vincent and B. A. Buscher, Identification of non-Dot/Icm suppressors of the Legionella pneumophila DeltadotL lethality phenotype, J Bacteriol, vol.188, issue.23, pp.8231-8243, 2006.

C. D. Vincent and J. R. Friedman, Identification of the core transmembrane complex of the Legionella Dot/Icm type IV secretion system, Mol Microbiol, vol.62, issue.5, pp.1278-1291, 2006.

C. D. Vincent, J. R. Friedman, K. C. Jeong, M. C. Sutherland, and J. P. Vogel, Identification of the DotL coupling protein subcomplex of the Legionella Dot/Icm type IV secretion system, Mol Microbiol, vol.85, issue.2, pp.378-391, 2012.

C. D. Vincent and J. P. Vogel, The Legionella pneumophila IcmS-LvgA protein complex is important for Dot/Icm-dependent intracellular growth, Mol Microbiol, vol.61, issue.3, pp.596-613, 2006.

M. Watarai, H. L. Andrews, and R. R. Isberg, Formation of a fibrous structure on the surface of Legionella pneumophila associated with exposure of DotH and DotO proteins after intracellular growth, Mol Microbiol, vol.39, issue.2, pp.313-329, 2001.

X. Xia, DAMBE6: new tools for microbial genomics, phylogenetics, and molecular evolution, J Hered, vol.108, issue.4, pp.431-437, 2017.

J. Xu, Structural insights into the roles of the IcmS-IcmW complex in the type IVb secretion system of Legionella pneumophila, Proc Natl Acad Sci U S A, vol.114, issue.51, pp.13543-13548, 2017.

D. S. Zamboni, S. Mcgrath, M. Rabinovitch, and C. R. Roy, Coxiella burnetii express type IV secretion system proteins that function similarly to components of the Legionella pneumophila Dot/Icm system, Mol Microbiol, vol.49, issue.4, pp.965-976, 2003.

W. Zhu, Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila, PLoS One, vol.6, issue.3, p.17638, 2011.

W. Zhu and Z. Q. Luo, Methods for determining protein translocation by the Legionella pneumophila Dot/Icm type IV secretion system, Methods Mol Biol, vol.954, pp.323-332, 2013.