Abstract
Legionella pneumophila is an intracellular pathogen that causes a severe pneumonia called Legionnaires’ disease that is often fatal when not promptly diagnosed and treated. However, L. pneumophila is mainly an environmental pathogen of protozoa. This bacterium parasitizes free-living amoeba and other aquatic protozoa with which it co-evolved over an evolutionary long time. Due to the close relationship between hosts and pathogens, their co-evolution leads to molecular interactions such as the exchange of genetic material through horizontal gene transfer (HGT). Those genes that confer an advantage to the bacteria were fixed in their genomes and help these pathogens to subvert host functions to their advantage. Genome sequencing of L. pneumophila and recently of the entire genus Legionella that comprises over 60 species revealed that Legionellae have co-opted genes and thus cellular functions from their eukaryotic hosts to a surprisingly high extent never observed before for an prokaryotic organism. Acquisition and loss of these eukaryotic-like genes and eukaryotic domains is an ongoing process underlining the highly dynamic nature of the Legionella genomes. Although the large amount and diversity of HGT that occurred between Legionella and their protozoan hosts seems to be unique in the prokaryotic world, the analyses of more and more genomes from environmental organisms and symbionts of amoeba revealed that such genetic exchanges occur among all amoeba-associated bacteria and also among the different microorganisms that infect amoeba such as viruses. This dynamic reshuffling and gene-acquisition has led to the emergence of major human pathogens such as Legionella and may lead to the emergence of new human pathogens from the environment.
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References
Ochiai K, Yamanaka T, Kimura K, Sawada O. Inheritance of drug resistance (and its transfer) between Shigella strains and between Shigella and E. coli strains. Hihon Iji Shimpor (in Japanese). 1959:34.
Boto L. Horizontal gene transfer in evolution: facts and challenges. Proc Biol Sci. 2010;277:819–27.
McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA, Dowdle WR. Legionnaires’ disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N Engl J Med. 1977;297:1197–203.
Newton HJ, Ang DK, van Driel IR, Hartland EL. Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev. 2010;23:274–98.
Rowbotham TJ. Preliminary report on the pathogenicity of Legionella pneumophila for freshwater and soil amoebae. J Clin Pathol. 1980;33:1179–83.
Horwitz MA, Silverstein SC. Legionnaires’ disease bacterium (Legionella pneumophila) multiples intracellularly in human monocytes. J Clin Invest. 1980;66:441–50.
Nash TW, Libby DM, Horwitz MA. Interaction between the legionnaires’ disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone. J Clin Invest. 1984;74:771–82.
Berger KH, Isberg RR. Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol. 1993;7:7–19.
Marra A, Blander SJ, Horwitz MA, Shuman HA. Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc Natl Acad Sci USA. 1992;89:9607–11.
Escoll P, Rolando M, Gomez-Valero L, Buchrieser C. From amoeba to macrophages: exploring the molecular mechanisms of Legionella pneumophila infection in both hosts. Curr Top Microbiol Immunol. 2013;376:1–34.
Hubber A, Roy CR. Modulation of host cell function by Legionella pneumophila type IV effectors. Annu Rev Cell Dev Biol. 2010;26:261–83.
Isberg RR, O’Connor TJ, Heidtman M. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat Rev Microbiol. 2009;7:13–24.
Cazalet C, Rusniok C, Bruggemann H, Zidane N, Magnier A, Ma L, et al. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat Genet. 2004;36:1165–73.
Nagai H, Kagan JC, Zhu X, Kahn RA, Roy CR. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science. 2002;295:679–82.
Rolando M, Buchrieser C. Post-translational modifications of host proteins by Legionella pneumophila: a sophisticated survival strategy. Future Microbiol. 2012;7:369–81.
Kubori T, Hyakutake A, Nagai H. Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol Microbiol. 2008;67:1307–19.
Price CT, Al-Khodor S, Al-Quadan T, Santic M, Habyarimana F, Kalia A, et al. Molecular mimicry by an F-Box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa. PLoS Pathog. 2009;5:e1000704.
Ivanov SS, Charron G, Hang HC, Roy CR. Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins. J Biol Chem. 2010;285:34686–98.
Price CT, Al-Quadan T, Santic M, Jones SC, Abu Kwaik Y. Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila. J Exp Med. 2010;207:1713–26.
DebRoy S, Dao J, Soderberg M, Rossier O, Cianciotto NP. Legionella pneumophila type II secretome reveals unique exoproteins and a chitinase that promotes bacterial persistence in the lung. Proc Natl Acad Sci USA. 2006;103:19146–51.
Lifshitz Z, Burstein D, Peeri M, Zusman T, Schwartz K, Shuman HA, et al. Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal. Proc Natl Acad Sci USA. 2013;110:E707–15.
Zhu W, Banga S, Tan Y, Zheng C, Stephenson R, Gately J, et al. Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila. PLoS ONE. 2011;6:e17638.
Crabill E, Schofield WB, Newton HJ, Goodman AL, Roy CR. Dot/Icm-translocated proteins important for biogenesis of the Coxiella burnetii-containing vacuole identified by screening of an effector mutant sublibrary. Infect Immun. 2018;86:e00758–17.
O’Connor TJ, Adepoju Y, Boyd D, Isberg RR. Minimization of the Legionella pneumophila genome reveals chromosomal regions involved in host range expansion. Proc Natl Acad Sci USA. 2011;108:14733–40.
Bacigalupe R, Lindsay D, Edwards G, Fitzgerald JR. Population genomics of Legionella longbeachae and hidden complexities of infection source attribution. Emerg Infect Dis. 2017;23:750–7.
Cazalet C, Gomez-Valero L, Rusniok C, Lomma M, Dervins-Ravault D, Newton HJ, et al. Analysis of the Legionella longbeachae genome and transcriptome uncovers unique strategies to cause Legionnaires’ disease. PLoS Genet. 2010;6:e1000851.
Burstein D, Amaro F, Zusman T, Lifshitz Z, Cohen O, Gilbert JA, et al. Genomic analysis of 38 Legionella species identifies large and diverse effector repertoires. Nat Genet. 2016;48:167–75.
Gomez-Valero L, Rusniok C, Carson D, Mondino S, Perez-Cobas AE, Rolando M, et al. More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells. Proc Natl Acad Sci USA. 2019;116:2265–73.
Riedmaier P, Sansom FM, Sofian T, Beddoe T, Schuelein R, Newton HJ, et al. Multiple ecto-nucleoside triphosphate diphosphohydrolases facilitate intracellular replication of Legionella pneumophila. Biochem J. 2014;462:279–89.
Summers EL, Cumming MH, Oulavallickal T, Roberts NJ, Arcus VL. Structures and kinetics for plant nucleoside triphosphate diphosphohydrolases support a domain motion catalytic mechanism. Protein Sci. 2017;26:1627–38.
Rolando M, Sanulli S, Rusniok C, Gomez-Valero L, Bertholet C, Sahr T, et al. Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication. Cell Host Microbe. 2013;13:395–405.
de Felipe KS, Pampou S, Jovanovic OS, Pericone CD, Ye SF, Kalachikov S, et al. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J Bacteriol. 2005;187:7716–26.
Gomez Valero L, Runsiok C, Cazalet C,CB. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front Microbiol. 2011;2:208.
Lurie-Weinberger MN, Gomez-Valero L, Merault N, Glockner G, Buchrieser C, Gophna U. The origins of eukaryotic-like proteins in Legionella pneumophila. Int J Med Microbiol. 2010;300:470–81.
Ensminger AW. Legionella pneumophila, armed to the hilt: justifying the largest arsenal of effectors in the bacterial world. Curr Opin Microbiol. 2016;29:74–80.
Escoll P, Mondino S, Rolando M, Buchrieser C. Targeting of host organelles by pathogenic bacteria: a sophisticated subversion strategy. Nat Rev Microbiol. 2016;14:5–19.
Gomez-Valero L, Rusniok C, Cazalet C, Buchrieser C. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front Microbiol. 2011;2:208.
Qiu J, Luo ZQ. Legionella and Coxiella effectors: strength in diversity and activity. Nat Rev Microbiol. 2017;15:591–605.
Rolando M, Buchrieser C. Legionella pneumophila type IV effectors hijack the transcription and translation machinery of the host cell. Trends Cell Biol. 2014;24:771–8.
Barlocher K, Welin A, Hilbi H. Formation of the Legionella replicative compartment at the crossroads of retrograde trafficking. Front Cell Infect Microbiol. 2017;7:482.
Merrill AH, Sandhoff K. Sphingolipids: metabolism and cell signalling In: Vance DE, Vance JE, editors. Biochemistry of lipids, lipoproteins and membranes, Vol. 36. Elsevier Science: Amsterdam; 2002. p. 373−407.
Heung JL, Luberto C, Del Poeta M. Role of sphingolipids in microbial pathogenesis. Infect Immun. 2006;74:28–39.
Shabardina V, Kischka T, Kmita H, Suzuki Y, Makalowski W. Environmental adaptation of Acanthamoeba castellanii and Entamoeba histolytica at genome level as seen by comparative genomic analysis. Int J Biol Sci. 2018;14:306–20.
Rolando M, Escoll P, Buchrieser C. Legionella pneumophila restrains autophagy by modulating the host’s sphingolipid metabolism. Autophagy. 2016;12:1053–4.
Rolando M, Escoll P, Nora T, Botti J, Boitez V, Bedia C, et al. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. Proc Natl Acad Sci USA. 2016;113:1901–6.
Degtyar E, Zusman T, Ehrlich M, Segal GA. Legionella effector acquired from protozoa is involved in sphingolipids metabolism and is targeted to the host cell mitochondria. Cell Microbiol. 2009;11:1219–35.
Gomez-Valero L, Buchrieser C. Genome dynamics in Legionella: the basis of versatility and adaptation to intracellular replication. Cold Spring Harb Perspect Med. 2013;3:a009993.
Choy A, Dancourt J, Mugo B, O’Connor TJ, Isberg RR, Melia TJ, et al. The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science. 2012;338:1072–6.
Schmitz-Esser S, Tischler P, Arnold R, Montanaro J, Wagner M, Rattei T, et al. The genome of the amoeba symbiont “Candidatus Amoebophilus asiaticus” reveals common mechanisms for host cell interaction among amoeba-associated bacteria. J Bacteriol. 2010;192:1045–57.
Casadevall A, Fu MS, Guimaraes AJ, Albuquerque P. The ‘amoeboid predator-fungal animal virulence’ hypothesis. J Fungi (Basel). 2019;5:E10.
Raoult D, Audic S, Robert C, Abergel C, Renesto P, Ogata H, et al. The 1.2-megabase genome sequence of Mimivirus. Science. 2004;306:1344–50.
Moreira D, Brochier-Armanet C. Giant viruses, giant chimeras: the multiple evolutionary histories of Mimivirus genes. BMC Evol Biol. 2008;8:12.
Ogata H, La Scola B, Audic S, Renesto P, Blanc G, Robert C, et al. Genome sequence of Rickettsia bellii illuminates the role of amoebae in gene exchanges between intracellular pathogens. PLoS Genet. 2006;2:e–76.
Gomez-Valero L, Neou Bonora M, Gribaldo S, Buchrieser C. Interdomain horizontal gene transfer shaped the genomes of Legionella pneumophila and Legionella longbeachae. In: Gophna U, editor. Lateral gene transfer in evolution. New York, NY: Springer; 2013. p. 199−219.
Nyvltova E, Sut’ak R, Zarsky V, Harant K, Hrdy I, Tachezy J. Lateral gene transfer of p-cresol- and indole-producing enzymes from environmental bacteria to Mastigamoeba balamuthi. Environ Microbiol. 2017;19:1091–102.
Kaneko T, Stogios PJ, Ruan X, Voss C, Evdokimova E, Skarina T, et al. Identification and characterization of a large family of superbinding bacterial SH2 domains. Nat Commun. 2018;9:4549.
de Felipe KS, Glover RT, Charpentier X, Anderson OR, Reyes M, Pericone CD, et al. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog. 2008;4:e1000117.
Gimenez G, Bertelli C, Moliner C, Robert C, Raoult D, Fournier PE, et al. Insight into cross-talk between intra-amoebal pathogens. BMC Genom. 2011;12:542.
Gomez-Valero L, Rusniok C, Jarraud S, Vacherie B, Rouy Z, Barbe V, et al. Extensive recombination events and horizontal gene transfer shaped the Legionella pneumophila genomes. BMC Genom. 2011;12:536.
Wang Z, Wu M. Comparative genomic analysis of Acanthamoeba endosymbionts highlights the role of amoebae as a “melting pot” shaping the Rickettsiales evolution. Genome Biol Evol. 2017;9:3214–24.
Bertelli C, Greub G. Lateral gene exchanges shape the genomes of amoeba-resisting microorganisms. Front Cell Infect Microbiol. 2012;2:110.
Buchrieser C, Charpentier X. Induction of competence for natural transformation in Legionella pneumophila and exploitation for mutant construction. Methods Mol Biol. 2013;954:183–95.
Acknowledgements
Work in the CB laboratory is financed by the Institut Pasteur and has received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID) and grant ANR 15 CE17 0014 03.
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Gomez-Valero, L., Buchrieser, C. Intracellular parasitism, the driving force of evolution of Legionella pneumophila and the genus Legionella. Genes Immun 20, 394–402 (2019). https://doi.org/10.1038/s41435-019-0074-z
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DOI: https://doi.org/10.1038/s41435-019-0074-z
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