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Review

Post-Translational Modifications of Host Proteins by Legionella Pneumophila: A Sophisticated Survival Strategy

Monica Rolando1 Institut Pasteur, Biologie des Bactéries Intracellulaires, 75724Paris, France.;2 CNRS UMR 3525, 75724Paris, FranceView further author information
&
Carmen Buchrieser1 Institut Pasteur, Biologie des Bactéries Intracellulaires, 75724Paris, France.;2 CNRS UMR 3525, 75724Paris, FranceCorrespondence[email protected]
View further author information
Pages 369-381 | Published online: 06 Mar 2012

References

  • Fraser DW , TsaiTR, OrensteinW et al. Legionnaires‘ disease: description of an epidemic of pneumonia. N. Engl. J. Med. 297(22) , 1189–1197 (1977).
  • Horwitz MA , SilversteinSC. Legionnaires‘ disease bacterium (Legionella pneumophila) multiples intracellularly in human monocytes. J. Clin. Invest.66(3) , 441–450 (1980).
  • Nash TW , LibbyDM, HorwitzMA. Interaction between the Legionnaires‘ disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone. J. Clin. Invest.74(3) , 771–782 (1984).
  • Rowbotham TJ . Preliminary report on the pathogenicity of Legionella pneumophila for freshwater and soil amoebae. J. Clin. Pathol.33(12) , 1179–1183 (1980).
  • Segal G , PurcellM, ShumanHA. 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. USA95(4) , 1669–1674 (1998).
  • Segal G , ShumanHA. Legionella pneumophila utilizes the same genes to multiply within Acanthamoeba castellanii and human macrophages. Infect. Immun.67(5) , 2117–2124 (1999).
  • Vogel JP , AndrewsHL, WongSK, IsbergRR. Conjugative transfer by the virulence system of Legionella pneumophila. Science279(5352) , 873–876 (1998).
  • Berger KH , IsbergRR. Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol. Microbiol.7(1) , 7–19 (1993).
  • Marra A , BlanderSJ, HorwitzMA, ShumanHA. Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc. Natl Acad. Sci. USA89(20) , 9607–9611 (1992).
  • Burstein D , ZusmanT, DegtyarE, VinerR, SegalG, PupkoT. Genome-scale identification of Legionella pneumophila effectors using a machine learning approach. PLoS Pathog.5(7) , E1000508 (2009).
  • Campodonico EM , ChesnelL, RoyCR. A yeast genetic system for the identification and characterization of substrate proteins transferred into host cells by the Legionella pneumophila Dot/Icm system. Mol. Microbiol.56(4) , 918–933 (2005).
  • De Felipe KS , GloverRT, CharpentierX et al. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog.4(8) , E1000117 (2008).
  • De Felipe KS , PampouS, JovanovicOS et al. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 187(22) , 7716–7726 (2005).
  • Heidtman M , ChenEJ, MoyMY, IsbergRR. Large-scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways. Cell. Microbiol.11(2) , 230–248 (2009).
  • Shohdy N , EfeJA, EmrSD, ShumanHA. Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking. Proc. Natl Acad. Sci. USA102(13) , 4866–4871 (2005).
  • Zhu W , BangaS, TanY et al. Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila. PLoS One 6(3) , E17638 (2011).
  • Cazalet C , RusniokC, BruggemannH et al. Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat. Genet. 36(11) , 1165–1173 (2004).
  • Chien M , MorozovaI, ShiS et al. The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305(5692) , 1966–1968 (2004).
  • Mostowy S , CossartP. From pathogenesis to cell biology and back. Cell Host Microbe5(6) , 510–513 (2009).
  • Hubber A , RoyCR. Modulation of host cell function by Legionella pneumophila type IV effectors. Annu. Rev. Cell. Dev. Biol.26 , 261–283 (2010).
  • Isberg RR , O‘ConnorTJ, HeidtmanM. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat. Rev. Microbiol.7(1) , 13–24 (2009).
  • Nora T , LommaM, Gomez-ValeroL, BuchrieserC. Molecular mimicry: an important virulence strategy employed by Legionella pneumophila to subvert host functions. Future Microbiol.4 , 691–701 (2009).
  • Jensen ON . Interpreting the protein language using proteomics. Nat. Rev. Mol. Cell. Biol.7(6) , 391–403 (2006).
  • Ribet D , CossartP. Pathogen-mediated posttranslational modifications: a re-emerging field. Cell143(5) , 694–702 (2011).
  • Finley D . Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem.78 , 477–513 (2009).
  • Pickart CM , CohenRE. Proteasomes and their kin: proteases in the machine age. Nat. Rev. Mol. Cell. Biol.5(3) , 177–187 (2004).
  • Clague MJ , UrbéS. Ubiquitin: same molecule, different degradation pathways. Cell143(5) , 682–685 (2010).
  • Pickart CM , FushmanD. Polyubiquitin chains: polymeric protein signals. Curr. Opin. Chem. Biol.8(6) , 610–616 (2004).
  • Weissman AM . Themes and variations on ubiquitylation. Nat. Rev. Mol. Cell. Biol.2(3) , 169–178 (2001).
  • Lee I , SchindelinH. Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes. Cell134(2) , 268–278 (2008).
  • Van Wijk SJ , TimmersHT. The family of ubiquitin–conjugating enzymes (E2s): deciding between life and death of proteins. FASEB J.24(4) , 981–993 (2010).
  • Ardley HC , RobinsonPA. E3 ubiquitin ligases. Essays Biochem.41 , 15–30 (2005).
  • Marín I . Animal HECT ubiquitin ligases: evolution and functional implications. BMC Evol. Biol.10 , 56 (2010).
  • Rotin D , KumarS. Physiological functions of the HECT family of ubiquitin ligases. Nat. Rev. Mol. Cell. Biol.10(6) , 398–409 (2009).
  • Budhidarmo R , NakataniY, DayCL. RINGs hold the key to ubiquitin transfer. Trends Biochem. Sci.37(2) , 58–65 (2012).
  • Hatakeyama S , YadaM, MatsumotoM, IshidaN, NakayamaKI. U box proteins as a new family of ubiquitin-protein ligases. J. Biol. Chem.276(35) , 33111–33120 (2001).
  • Komander D , ClagueMJ, UrbeS. Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell. Biol.10 , 550–563 (2009).
  • Rytkonen A , HoldenDW. Bacterial interference of ubiquitination and deubiquitination. Cell Host Microbe1(1) , 13–22 (2007).
  • Zhang Y , HigashideWM, McCormickBA, ChenJ, ZhouD. The inflammation-associated Salmonella SopA is a HECT-like E3 ubiquitin ligase. Mol. Microbiol.62(3) , 786–793 (2006).
  • Rohde JR , BreitkreutzA, ChenalA, SansonettiPJ, ParsotC. Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell Host Microbe1(1) , 77–83 (2007).
  • Le Negrate G , FaustinB, WelshK et al. Salmonella secreted factor L deubiquitinase of Salmonella typhimurium inhibits NF-kappaB, suppresses IkappaBalpha ubiquitination and modulates innate immune responses. J. Immunol.80(7) , 5045–5056 (2008).
  • Kubori T , HyakutakeA, NagaiH. Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol. Microbiol.67(6) , 1307–1319 (2008).
  • Kubori T , ShinzawaN, KanukaH, NagaiH. Legionella metaeffector exploits host proteasome to temporally regulate cognate effector. PLoS Pathog.6(12) , E1001216 (2010).
  • Lorick KL , JensenJP, FangS, OngAM, HatakeyamaS, WeissmanAM. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl Acad. Sci. USA96(20) , 11364–11369 (1999).
  • Feldman RM , CorrellCC, KaplanKB, DeshaiesRJ. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell91(2) , 221–230 (1997).
  • Skowyra D , CraigKL, TyersM, ElledgeSJ, HarperJW. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell91(2) , 209–219 (1997).
  • Skaar JR , D‘AngiolellaV, PaganJK, PaganoM. SnapShot: F box proteins II. Cell137(7) , 1358.E1 (2009).
  • Skaar JR , PaganJK, PaganoM. SnapShot: F box proteins I. Cell137(6) , 1160.E1 (2009).
  • Angot A , VergunstA, GeninS, PeetersN. Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems. PLoS Pathog.3(1) , E3 (2007).
  • Dorer MS , KirtonD, BaderJS, IsbergRR. RNA interference analysis of Legionella in Drosophila cells: exploitation of early secretory apparatus dynamics. PLoS Pathog.2(4) , E34 (2006).
  • Al-Khodor S , PriceCT, HabyarimanaF, KaliaA, Abu Kwaik Y. A Dot/Icm-translocated ankyrin protein of Legionella pneumophila is required for intracellular proliferation within human macrophages and protozoa. Mol. Microbiol.70(4) , 908–923 (2008).
  • Lomma M , Dervins-RavaultD, RolandoM et al. The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. Cell. Microbiol. 12(9) , 1272–1291 (2010).
  • Price CT , Al-KhodorS, Al-QuadanT et al. Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa. PLoS Pathog. 5(12) , E1000704 (2009).
  • Olski TM , NoegelAA, KorenbaumE. Parvin, a 42 kDa focal adhesion protein, related to the alpha-actinin superfamily. J. Cell Sci.114(Pt 3) , 525–538 (2001).
  • Yamaji S , SuzukiA, SugiyamaY et al. A novel integrin-linked kinase-binding protein, affixin, is involved in the early stage of cell-substrate interaction. J. Cell Biol. 153(6) , 1251–1264 (2001).
  • Sepulveda JL , WuC. The parvins. Cell. Mol. Life Sci.63(1) , 25–35 (2006).
  • Ensminger AW , IsbergRR. E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates. Infect. Immun.78(9) , 3905–3919 (2010).
  • Ivanov SS , RoyCR. Modulation of ubiquitin dynamics and suppression of DALIS formation by the Legionella pneumophila Dot/Icm system. Cell. Microbiol.11(2) , 261–278 (2009).
  • Canadien V , TanT, ZilberR, SzetoJ, PerrinAJ, BrumellJH. Cutting edge: microbial products elicit formation of dendritic cell aggresome-like induced structures in macrophages. J. Immunol.174(5) , 2471–2475 (2005).
  • Ivanov SS , CharronG, HangHC, RoyCR. Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins. J. Biol. Chem.285(45) , 34686–34698 (2010).
  • Price CT , Al-QuadanT, SanticM, JonesSC, Abu Kwaik Y. Exploitation of conserved eukaryotic host cell farnesylation machinery by an F-box effector of Legionella pneumophila. J. Exp. Med.207(8) , 1713–1726 (2010).
  • Wright LP , PhilipsMR. Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J. Lipid Res.47(5) , 883–891 (2006).
  • Al-Quadan T , PriceCT, LondonN, Schueler-FurmanO, Abu Kwaik Y. Anchoring of bacterial effectors to host membranes through host-mediated lipidation by prenylation: a common paradigm. Trends Microbiol.19(12) , 573–579 (2011).
  • Price CT , JonesSC, AmundsonKE, KwaikYA. Host-mediated post-translational prenylation of novel Dot/Icm-translocated effectors of Legionella pneumophila. Front. Microbiol.1 , 131 (2010).
  • Price CT , KwaikYA. Exploitation of host polyubiquitination machinery through molecular mimicry by eukaryotic-like bacterial F-Box effectors. Front. Microbiol.1 , 122 (2010).
  • Price CT , Al-QuadanT, SanticM, RosenshineI, Abu Kwaik Y. Host proteasomal degradation generates amino acids essential for intracellular bacterial growth. Science334(6062) , 1553–1557 (2011).
  • Hunter T . Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell80(2) , 225–236 (1995).
  • Juris SJ , RudolphAE, HuddlerD, OrthK, DixonJE. A distinctive role for the Yersinia protein kinase: actin binding, kinase activation, and cytoskeleton disruption. Proc. Natl Acad. Sci. USA97(17) , 9431–9436 (2000).
  • Juris SJ , ShahK, ShokatK, DixonJE, VacratsisPO. Identification of otubain 1 as a novel substrate for the Yersinia protein kinase using chemical genetics and mass spectrometry. FEBS Lett.580(1) , 179–183 (2006).
  • Gomez-Valero L , RusniokC, JarraudS et al. Extensive recombination events and horizontal gene transfer shaped the Legionella pneumophila genomes. BMC Genomics 12 , 536 (2011).
  • Ge J , XuH, LiT et al. A Legionella type IV effector activates the NF-kappaB pathway by phosphorylating the IkappaB family of inhibitors. Proc. Natl Acad. Sci. USA 106(33) , 13725–13730 (2009).
  • Karin M , LinA. NF-kappaB at the crossroads of life and death. Nat. Immunol.3(3) , 221–227 (2002).
  • Bartfeld S , EngelsC, BauerB et al. Temporal resolution of two-tracked NF-kappaB activation by Legionella pneumophila. Cell. Microbiol. 11(11) , 1638–1651 (2009).
  • Losick VP , HaensslerE, MoyMY, IsbergRR. LnaB: a Legionella pneumophila activator of NF-kappaB. Cell. Microbiol.12(8) , 1083–1097 (2010).
  • Hervet E , CharpentierX, VianneyA et al. Protein kinase LegK2 is a type IV secretion system effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila. Infect. Immun. 79(5) , 1936–1950 (2011).
  • Haenssler E , IsbergRR. Control of host cell phosphorylation by Legionella pneumophila. Front. Microbiol.2 , 64 (2011).
  • Lairson LL , HenrissatB, DaviesGJ, WithersSG. Glycosyltransferases: structures, functions, and mechanisms. Annu. Rev. Biochem.77 , 521–555 (2008).
  • Jank T , AktoriesK. Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol.16(5) , 222–229 (2008).
  • Belyi I , PopoffMR, CianciottoNP. Purification and characterization of a UDP-glucosyltransferase produced by Legionella pneumophila. Infect. Immun.71(1) , 181–186 (2003).
  • Belyi Y , NiggewegR, OpitzB et al. Legionella pneumophila glucosyltransferase inhibits host elongation factor 1A. Proc. Natl Acad. Sci. USA103(45) , 16953–16958 (2006).
  • Mateyak MK , KinzyTG. eEF1A: thinking outside the ribosome. J. Biol. Chem.285(28) , 21209–21213 (2010).
  • Aktories K . Bacterial protein toxins that modify host regulatory GTPases. Nat. Rev. Microbiol.9(7) , 487–498 (2011).
  • Belyi Y , TabakovaI, StahlM, AktoriesK. Lgt: a family of cytotoxic glucosyltransferases produced by Legionella pneumophila. J. Bacteriol.190(8) , 3026–3035 (2008).
  • Shen X , BangaS, LiuY et al. Targeting eEF1A by a Legionella pneumophila effector leads to inhibition of protein synthesis and induction of host stress response. Cell. Microbiol. 11(6) , 911–926 (2009).
  • Fontana MF , BangaS, BarryKC et al. Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila. PLoS Pathog. 7(2) , E1001289 (2011).
  • Massis LM , ZamboniDS. Innate immunity to Legionella pneumophila. Front. Microbiol.2 , 109 (2011).
  • Belyi Y , JankT, AktoriesK. Effector glycosyltransferases in Legionella. Front. Microbiol.2 , 76 (2011).
  • Worby CA , MattooS, KrugerRP et al. The fic domain: regulation of cell signaling by adenylylation. Mol. Cell 34(1) , 93–103 (2009).
  • Yarbrough ML , LiY, KinchLN, GrishinNV, BallHL, OrthK. AMPylation of Rho GTPases by Vibrio VopS disrupts effector binding and downstream signaling. Science323(5911) , 269–272 (2009).
  • Roy CR , MukherjeeS. Bacterial Fic proteins AMP up infection. Sci. Signal.2(62) , PE14 (2009).
  • Müller MP , PetersH, BlümerJ, BlankenfeldtW, GoodyRS, ItzenA. The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science329(5994) , 946–949 (2010).
  • Brombacher E , UrwylerS, RagazC et al. Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol-phosphate-binding effector protein of Legionella pneumophila. J. Biol. Chem. 284(8) , 4846–4856 (2009).
  • Sprang SR . G protein mechanisms: insights from structural analysis. Annu. Rev. Biochem.66 , 639–678 (1997).
  • Ingmundson A , DelpratoA, LambrightDG, RoyCR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature450(7168) , 365–369 (2007).
  • Machner MP , IsbergRR. A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science318(5852) , 974–977 (2007).
  • Schoebel S , OesterlinLK, BlankenfeldtW, GoodyRS, ItzenA. RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol. Cell36(6) , 1060–1072 (2009).
  • Neunuebel MR , ChenY, GasparAH, BacklundPS Jr, Yergey A, Machner MP. De-AMPylation of the small GTPase Rab1 by the Pathogen Legionella pneumophila. Science333(6041) , 453–456 (2011).
  • Tan Y , LuoZQ. Legionella pneumophila SidD is a deAMPylase that modifies Rab1. Nature475(7357) , 506–509 (2011).
  • Kagan JC , SteinMP, PypaertM, RoyCR. Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle. J. Exp. Med.199(9) , 1201–1211 (2004).
  • Derré I , IsbergRR. Legionella pneumophila replication vacuole formation involves rapid recruitment of proteins of the early secretory system. Infect. Immun.72(5) , 3048–3053 (2004).
  • Rigden DJ . Identification and modelling of a PPM protein phosphatase fold in the Legionella pneumophila deAMPylase SidD. FEBS Lett.585(17) , 2749–2754 (2011).
  • Kinch LN , YarbroughML, OrthK, GrishinNV. Fido, a novel AMPylation domain common to fic, doc, and AvrB. PLoS One4(6) , E5818 (2009).
  • Komano T , UtsumiR, KawamukaiM. Functional analysis of the fic gene involved in regulation of cell division. Res. Microbiol.142(2–3) , 269–277 (1991).
  • Zekarias B , MattooS, WorbyC, LehmannJ, RosenbuschRF, CorbeilLB. Histophilus somni IbpA DR2/Fic in virulence and immunoprotection at the natural host alveolar epithelial barrier. Infect. Immun.78(5) , 1850–1858 (2010).
  • Palanivelu DV , GoepfertA, MeuryM, GuyeP, DehioC, SchirmerT. Fic domain-catalyzed adenylylation: insight provided by the structural analysis of the type IV secretion system effector BepA. Protein Sci.20(3) , 492–499 (2011).
  • Pan X , LührmannA, SatohA, Laskowski-ArceMA, RoyCR. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science320(5883) , 1651–1654 (2008).
  • Mukherjee S , LiuX, ArasakiK, McdonoughJ, GalánJE, RoyCR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature477(7362) , 103–106 (2011).
  • Tan Y , ArnoldRJ, LuoZQ. Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. Proc. Natl Acad. Sci. USA108(52) , 21212–21217 (2011).
  • Kubori T , NagaiA. Bacterial effector-involved temporal and spatial regulation by hijack of the host ubiquitin pathway. Front. Microbiol.2 , 145 (2011).

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