Advertisement

Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis

  • Anja Lührmann
  • Hayley J. Newton
  • Matteo Bonazzi
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 413)

Abstract

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which manifests in severe outbreaks and is associated with important health and economic burden. Moreover, C. burnetii belongs to the list of class B bioterrorism organisms, as it is an airborne and highly infective pathogen with remarkable resistance to environmental stresses. Detailed study of the host–pathogen interaction during C. burnetii infection has been hampered due to the obligate intracellular nature of this pathogen. However, the development of an axenic culture medium, together with the implementation of bioinformatics tools and high-content screening approaches, have significantly progressed C. burnetii research in the last decade. This has facilitated identification of the Dot/Icm type IV secretion system (T4SS) as an essential virulence factor. T4SS is used to deliver an arsenal of effector proteins into the cytoplasm of the host cell. These effectors mediate the survival of the host cell and the development of very large replicative compartments called Coxiella-containing vacuoles (CCVs). Biogenesis of the CCV relies on T4SS-dependent re-routing of numerous intracellular trafficking pathways to deliver membranes and nutrients that are essential for bacterial replication. This review aims to illustrate the key milestones that have contributed to ascribe C. burnetii as a model organism for the study of host/pathogen interactions as well as presenting an up-to-date description of our knowledge of the cell biology of C. burnetii infections.

Keywords

Coxiella burnetii Phagosome maturation Autophagy Cell death System biology In vivo models 

References

  1. Akporiaye ET, Rowatt JD, Aragon AA, Baca OG (1983) Lysosomal response of a murine macrophage-like cell line persistently infected with Coxiella burnetii. Infect Immun 40(3):1155–1162. PMCID: PMC348171Google Scholar
  2. Alvarez-Martinez CE, Christie PJ (2009) Biological diversity of prokaryotic type IV secretion systems. Microbiol Mol Biol Rev 73(4):775–808.  https://doi.org/10.1128/mmbr.00023-09CrossRefPubMedGoogle Scholar
  3. Angelakis E, Raoult D (2010) Q Fever Vet Microbiol 140(3–4):297–309.  https://doi.org/10.1016/j.vetmic.2009.07.016CrossRefPubMedGoogle Scholar
  4. Backert S, Meyer TF (2006) Type IV secretion systems and their effectors in bacterial pathogenesis. Curr Opin Microbiol 9(2):207–217.  https://doi.org/10.1016/j.mib.2006.02.008CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bastos RG, Howard ZP, Hiroyasu A, Goodman AG (2017) Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection. Infect Immun 85(7).  https://doi.org/10.1128/iai.00218-17CrossRefPubMedPubMedCentralGoogle Scholar
  6. Battisti JM, Watson LA, Naung MT, Drobish AM, Voronina E, Minnick MF (2017) Analysis of the Caenorhabditis elegans innate immune response to Coxiella burnetii. Innate Immun 23(2):111–127.  https://doi.org/10.1177/1753425916679255CrossRefPubMedGoogle Scholar
  7. Beare PA, Howe D, Cockrell DC, Omsland A, Hansen B, Heinzen RA (2009) Characterization of a Coxiella burnetii ftsZ mutant generated by Himar1 transposon mutagenesis. J Bacteriol 191(5):1369–1381.  https://doi.org/10.1128/JB.01580-08CrossRefPubMedPubMedCentralGoogle Scholar
  8. Beare PA, Gilk SD, Larson CL, Hill J, Stead CM, Omsland A, Cockrell DC, Howe D, Voth DE, Heinzen RA (2011) Dot/Icm type IVB secretion system requirements for Coxiella burnetii growth in human macrophages. MBio 2(4):e00175–00111.  https://doi.org/10.1128/mBio.00175-11CrossRefPubMedPubMedCentralGoogle Scholar
  9. Benenson AS, Tigertt WD (1956) Studies on Q fever in man. Trans Assoc Am Physicians 69:98–104 PMID: 13380951PubMedGoogle Scholar
  10. Bergsbaken T, Fink SL, Cookson BT (2009) Pyroptosis: host cell death and inflammation. Nat Rev Microbiol 7(2):99–109.  https://doi.org/10.1038/nrmicro2070CrossRefPubMedPubMedCentralGoogle Scholar
  11. Beron W, Gutierrez MG, Rabinovitch M, Colombo MI (2002) Coxiella burnetii localizes in a Rab7-labeled compartment with autophagic characteristics. Infect Immun 70(10):5816–5821.  https://doi.org/10.1128/IAI.70.10.5816-5821.2002CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bisle S, Klingenbeck L, Borges V, Sobotta K, Schulze-Luehrmann J, Menge C, Heydel C, Gomes JP, Lührmann A (2016) The inhibition of the apoptosis pathway by the Coxiella burnetii effector protein CaeA requires the EK repetition motif, but is independent of survivin. Virulence 7(4):400–412.  https://doi.org/10.1080/21505594.2016.1139280CrossRefPubMedPubMedCentralGoogle Scholar
  13. Bradley WP, Boyer MA, Nguyen HT, Birdwell LD, Yu J, Ribeiro JM, Weiss SR, Zamboni DS, Roy CR, Shin S (2016) Primary role for toll-like receptor-driven tumor necrosis factor rather than cytosolic immune detection in restricting Coxiella burnetii phase II replication within mouse macrophages. Infect Immun 84(4):998–1015.  https://doi.org/10.1128/IAI.01536-15CrossRefPubMedPubMedCentralGoogle Scholar
  14. Brooke RJ, Kretzschmar ME, Mutters NT, Teunis PF (2013) Human dose response relation for airborne exposure to Coxiella burnetii. BMC Infect Dis 13:488.  https://doi.org/10.1186/1471-2334-13-488CrossRefPubMedPubMedCentralGoogle Scholar
  15. Burton PR, Kordova N, Paretsky D (1971) Electron microscopic studies of the rickettsia Coxiella burnetii: entry, lysosomal response, and fate of rickettsial DNA in L-cells. Can J Microbiol 17(2):143–150 PMID: 4100953CrossRefPubMedGoogle Scholar
  16. Burton PR, Stueckemann J, Welsh RM, Paretsky D (1978) Some ultrastructural effects of persistent infections by the rickettsia Coxiella burnetii in mouse L cells and green monkey kidney (Vero) cells. Infect Immun 21(2):556–566. PMCID: PMC422031Google Scholar
  17. Carey KL, Newton HJ, Lührmann A, Roy CR (2011) The Coxiella burnetii Dot/Icm system delivers a unique repertoire of type IV effectors into host cells and is required for intracellular replication. PLoS Pathog 7(5):e1002056.  https://doi.org/10.1371/journal.ppat.1002056CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chandran Darbari V, Waksman G (2015) Structural biology of bacterial type IV secretion systems. Annu Rev Biochem 84:603–629.  https://doi.org/10.1146/annurev-biochem-062911-102821CrossRefPubMedPubMedCentralGoogle Scholar
  19. Chen C, Banga S, Mertens K, Weber MM, Gorbaslieva I, Tan Y, Luo ZQ, Samuel JE (2010) Large-scale identification and translocation of type IV secretion substrates by Coxiella burnetii. Proc Natl Acad Sci U S A 107(50):21755–21760.  https://doi.org/10.1073/pnas.1010485107CrossRefPubMedPubMedCentralGoogle Scholar
  20. Coleman SA, Fischer ER, Howe D, Mead DJ, Heinzen RA (2004) Temporal analysis of Coxiella burnetii morphological differentiation. J Bacteriol 186(21):7344–7352.  https://doi.org/10.1128/JB.186.21.7344-7352.2004CrossRefPubMedPubMedCentralGoogle Scholar
  21. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2(9):647–656.  https://doi.org/10.1038/nrc883CrossRefPubMedGoogle Scholar
  22. Cunha LD, Ribeiro JM, Fernandes TD, Massis LM, Khoo CA, Moffatt JH, Newton HJ, Roy CR, Zamboni DS (2015) Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA. Nat Commun 6:10205.  https://doi.org/10.1038/ncomms10205CrossRefPubMedPubMedCentralGoogle Scholar
  23. Czyz DM, Potluri LP, Jain-Gupta N, Riley SP, Martinez JJ, Steck TL, Crosson S, Shuman HA, Gabay JE (2014) Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens. MBio 5(4):e01534–01514.  https://doi.org/10.1128/mBio.01534-14CrossRefPubMedPubMedCentralGoogle Scholar
  24. Dellacasagrande J, Ghigo E, Hammami SM, Toman R, Raoult D, Capo C, Mege JL (2000) Alpha(v)beta(3) integrin and bacterial lipopolysaccharide are involved in Coxiella burnetii-stimulated production of tumor necrosis factor by human monocytes. Infect Immun 68(10):5673–5678. PMCID: PMC101522CrossRefPubMedPubMedCentralGoogle Scholar
  25. Delsing CE, Warris A, Bleeker-Rovers CP (2011) Q fever: still more queries than answers. Adv Exp Med Biol 719:133–143.  https://doi.org/10.1007/978-1-4614-0204-6_12CrossRefPubMedGoogle Scholar
  26. Eckart RA, Bisle S, Schulze-Luehrmann J, Wittmann I, Jantsch J, Schmid B, Berens C, Lührmann A (2014) Antiapoptotic activity of Coxiella burnetii effector protein AnkG is controlled by p32-dependent trafficking. Infect Immun 82(7):2763–2771.  https://doi.org/10.1128/IAI.01204-13CrossRefPubMedPubMedCentralGoogle Scholar
  27. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nat 391(6662):43–50.  https://doi.org/10.1038/34112CrossRefGoogle Scholar
  28. Fielden LF, Moffatt JH, Kang Y, Baker MJ, Khoo CA, Roy CR, Stojanovski D, Newton HJ (2017) A farnesylated Coxiella burnetii effector forms a multimeric complex at the mitochondrial outer membrane during infection. Infect Immun 85(5): https://doi.org/10.1128/iai.01046-16CrossRefPubMedPubMedCentralGoogle Scholar
  29. Flannagan RS, Jaumouille V, Grinstein S (2012) The cell biology of phagocytosis. Annu Rev Pathol 7:61–98.  https://doi.org/10.1146/annurev-pathol-011811-132445CrossRefPubMedGoogle Scholar
  30. Friedrich A, Pechstein J, Berens C, Lührmann A (2017) Modulation of host cell apoptotic pathways by intracellular pathogens. Curr Opin Microbiol 35:88–99.  https://doi.org/10.1016/j.mib.2017.03.001CrossRefPubMedGoogle Scholar
  31. Gallon M, Cullen PJ (2015) Retromer and sorting nexins in endosomal sorting. Biochem Soc Trans 43(1):33–47.  https://doi.org/10.1042/BST20140290CrossRefPubMedGoogle Scholar
  32. Gallucci S, Lolkema M, Matzinger P (1999) Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5(11):1249–1255.  https://doi.org/10.1038/15200CrossRefPubMedGoogle Scholar
  33. Ghosal D, Chang YW, Jeong KC, Vogel JP, Jensen GJ (2017) In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography. EMBO Rep.  https://doi.org/10.15252/embr.201643598CrossRefPubMedPubMedCentralGoogle Scholar
  34. Gilk SD (2012) Role of lipids in Coxiella burnetii infection. Adv Exp Med Biol 984:199–213.  https://doi.org/10.1007/978-94-007-4315-1_10CrossRefPubMedGoogle Scholar
  35. Gilk SD, Cockrell DC, Luterbach C, Hansen B, Knodler LA, Ibarra JA, Steele-Mortimer O, Heinzen RA (2013) Bacterial colonization of host cells in the absence of cholesterol. PLoS Pathog 9(1):e1003107.  https://doi.org/10.1371/journal.ppat.1003107CrossRefPubMedPubMedCentralGoogle Scholar
  36. Graham JG, MacDonald LJ, Hussain SK, Sharma UM, Kurten RC, Voth DE (2013) Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages. Cell Microbiol 15(6):1012–1025.  https://doi.org/10.1111/cmi.12096CrossRefPubMedPubMedCentralGoogle Scholar
  37. Graham JG, Winchell CG, Kurten RC, Voth DE (2016) Development of an Ex Vivo tissue platform to study the human lung response to Coxiella burnetii. Infect Immun 84(5):1438–1445.  https://doi.org/10.1128/IAI.00012-16CrossRefPubMedPubMedCentralGoogle Scholar
  38. Green DR, Llambi F (2015) Cell death signaling. Cold Spring Harb Perspect Biol 7(12).  https://doi.org/10.1101/cshperspect.a006080CrossRefPubMedPubMedCentralGoogle Scholar
  39. Grohmann E, Christie PJ, Waksman G, Backert S (2018) Type IV secretion in Gram-negative and Gram-positive bacteria. Mol Microbiol 107:455–471.  https://doi.org/10.1111/mmi.13896CrossRefPubMedGoogle Scholar
  40. Gutierrez MG, Vazquez CL, Munafo DB, Zoppino FC, Beron W, Rabinovitch M, Colombo MI (2005) Autophagy induction favours the generation and maturation of the Coxiella-replicative vacuoles. Cell Microbiol 7(7):981–993.  https://doi.org/10.1111/j.1462-5822.2005.00527.xCrossRefPubMedGoogle Scholar
  41. Hackstadt T, Williams JC (1981) Biochemical stratagem for obligate parasitism of eukaryotic cells by Coxiella burnetii. Proc Natl Acad Sci USA 78(5):3240–3244. PMCID: PMC319537CrossRefGoogle Scholar
  42. Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T (2013) Autophagosomes form at ER-mitochondria contact sites. Nat 495(7441):389–393.  https://doi.org/10.1038/nature11910CrossRefGoogle Scholar
  43. Harding CR, Schroeder GN, Reynolds S, Kosta A, Collins JW, Mousnier A, Frankel G (2012) Legionella pneumophila pathogenesis in the Galleria mellonella infection model. Infect Immun 80(8):2780–2790.  https://doi.org/10.1128/IAI.00510-12CrossRefPubMedPubMedCentralGoogle Scholar
  44. Heinzen RA, Scidmore MA, Rockey DD, Hackstadt T (1996) Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis. Infect Immun 64(3):796–809. PMCID: PMC173840Google Scholar
  45. Howe D, Heinzen RA (2005) Replication of Coxiella burnetii is inhibited in CHO K-1 cells treated with inhibitors of cholesterol metabolism. Ann NY Acad Sci 1063:123–129.  https://doi.org/10.1196/annals.1355.020CrossRefPubMedGoogle Scholar
  46. Howe D, Melnicakova J, Barak I, Heinzen RA (2003) Fusogenicity of the Coxiella burnetii parasitophorous vacuole. Ann NY Acad Sci 990:556–562.  https://doi.org/10.1111/j.1749-6632.2003.tb07426.xCrossRefPubMedGoogle Scholar
  47. Howe D, Shannon JG, Winfree S, Dorward DW, Heinzen RA (2010) Coxiella burnetii phase I and II variants replicate with similar kinetics in degradative phagolysosome-like compartments of human macrophages. Infect Immun 78(8):3465–3474.  https://doi.org/10.1128/IAI.00406-10CrossRefPubMedPubMedCentralGoogle Scholar
  48. Itakura E, Kishi-Itakura C, Mizushima N (2012) The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell 151(6):1256–1269.  https://doi.org/10.1016/j.cell.2012.11.001CrossRefPubMedPubMedCentralGoogle Scholar
  49. Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265(1):130–142.  https://doi.org/10.1111/imr.12287CrossRefPubMedPubMedCentralGoogle Scholar
  50. Justis AV, Hansen B, Beare PA, King KB, Heinzen RA, Gilk SD (2017) Interactions between the Coxiella burnetii parasitophorous vacuole and the endoplasmic reticulum involve the host protein ORP1L. Cell Microbiol 19(1).  https://doi.org/10.1111/cmi.12637CrossRefGoogle Scholar
  51. Kaur J, Debnath J (2015) Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol 16:461–472.  https://doi.org/10.1038/nrm4024CrossRefPubMedGoogle Scholar
  52. Kersh GJ (2013) Antimicrobial therapies for Q fever. Expert Rev Anti Infect Ther 11(11):1207–1214.  https://doi.org/10.1586/14787210.2013.840534CrossRefPubMedPubMedCentralGoogle Scholar
  53. Klingenbeck L, Eckart RA, Berens C, Lührmann A (2013) The Coxiella burnetii type IV secretion system substrate CaeB inhibits intrinsic apoptosis at the mitochondrial level. Cell Microbiol 15(4):675–687.  https://doi.org/10.1111/cmi.12066CrossRefPubMedGoogle Scholar
  54. Kohler LJ, Reed Sh C, Sarraf SA, Arteaga DD, Newton HJ, Roy CR (2016) Effector protein Cig2 decreases host tolerance of infection by directing constitutive fusion of autophagosomes with the Coxiella-containing vacuole. MBio 7(4): https://doi.org/10.1128/mbio.01127-16CrossRefPubMedPubMedCentralGoogle Scholar
  55. Lamkanfi M, Dixit VM (2010) Manipulation of host cell death pathways during microbial infections. Cell Host Microbe 8(1):44–54.  https://doi.org/10.1016/j.chom.2010.06.007CrossRefPubMedGoogle Scholar
  56. Larson CL, Beare PA, Howe D, Heinzen RA (2013) Coxiella burnetii effector protein subverts clathrin-mediated vesicular trafficking for pathogen vacuole biogenesis. Proc Natl Acad Sci USA 110(49):E4770–4779.  https://doi.org/10.1073/pnas.1309195110CrossRefPubMedPubMedCentralGoogle Scholar
  57. Larson CL, Martinez E, Beare PA, Jeffrey B, Heinzen RA, Bonazzi M (2016) Right on Q: genetics begin to unravel Coxiella burnetii host cell interactions. Future Microbiol 11:919–939.  https://doi.org/10.2217/fmb-2016-0044CrossRefPubMedPubMedCentralGoogle Scholar
  58. Latomanski EA, Newton P, Khoo CA, Newton HJ (2016) The effector Cig57 hijacks FCHO-mediated vesicular trafficking to facilitate intracellular replication of Coxiella burnetii. PLoS Pathog 12(12):e1006101.  https://doi.org/10.1371/journal.ppat.1006101CrossRefPubMedPubMedCentralGoogle Scholar
  59. Lührmann A, Roy CR (2007) Coxiella burnetii inhibits activation of host cell apoptosis through a mechanism that involves preventing cytochrome c release from mitochondria. Infect Immun 75(11):5282–5289.  https://doi.org/10.1128/IAI.00863-07CrossRefPubMedPubMedCentralGoogle Scholar
  60. Lührmann A, Nogueira CV, Carey KL, Roy CR (2010) Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proc Natl Acad Sci USA 107(44):18997–19001.  https://doi.org/10.1073/pnas.1004380107CrossRefPubMedPubMedCentralGoogle Scholar
  61. Luo J, Hu J, Zhang Y, Hu Q, Li S (2015) Hijacking of death receptor signaling by bacterial pathogen effectors. Apoptosis 20(2):216–223.  https://doi.org/10.1007/s10495-014-1068-yCrossRefPubMedGoogle Scholar
  62. Macdonald LJ, Graham JG, Kurten RC, Voth DE (2014) Coxiella burnetii exploits host cAMP-dependent protein kinase signalling to promote macrophage survival. Cell Microbiol 16(1):146–159.  https://doi.org/10.1111/cmi.12213CrossRefPubMedGoogle Scholar
  63. Madariaga MG, Rezai K, Trenholme GM, Weinstein RA (2003) Q fever: a biological weapon in your backyard. Lancet Infect Dis 3(11):709–721 PMID: 14592601CrossRefPubMedGoogle Scholar
  64. Maiuri MC, Le Toumelin G, Criollo A, Rain JC, Gautier F, Juin P, Tasdemir E, Pierron G, Troulinaki K, Tavernarakis N, Hickman JA, Geneste O, Kroemer G (2007) Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 26(10):2527–2539.  https://doi.org/10.1038/sj.emboj.7601689CrossRefPubMedPubMedCentralGoogle Scholar
  65. Man SM, Karki R, Kanneganti TD (2017) Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev 277(1):61–75.  https://doi.org/10.1111/imr.12534CrossRefPubMedPubMedCentralGoogle Scholar
  66. Mansilla Pareja ME, Bongiovanni A, Lafont F, Colombo MI (2017) Alterations of the Coxiella burnetii replicative vacuole membrane integrity and interplay with the autophagy pathway. Front Cell Infect Microbiol 7:112.  https://doi.org/10.3389/fcimb.2017.00112CrossRefPubMedPubMedCentralGoogle Scholar
  67. Marmion BP, Shannon M, Maddocks I, Storm P, Penttila I (1996) Protracted debility and fatigue after acute Q fever. Lancet 347(9006):977–978.  https://doi.org/10.1016/S0140-6736(96),91469-5CrossRefPubMedGoogle Scholar
  68. Martinez E, Cantet F, Fava L, Norville I, Bonazzi M (2014) Identification of OmpA, a Coxiella burnetii protein involved in host cell invasion, by multi-phenotypic high-content screening. PLoS Pathog 10(3):e1004013.  https://doi.org/10.1371/journal.ppat.1004013CrossRefPubMedPubMedCentralGoogle Scholar
  69. Martinez E, Allombert J, Cantet F, Lakhani A, Yandrapalli N, Neyret A, Norville IH, Favard C, Muriaux D, Bonazzi M (2016) Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development. Proc Natl Acad Sci USA 113(23):E3260–3269.  https://doi.org/10.1073/pnas.1522811113CrossRefPubMedPubMedCentralGoogle Scholar
  70. Maturana P, Graham JG, Sharma UM, Voth DE (2013) Refining the plasmid-encoded type IV secretion system substrate repertoire of Coxiella burnetii. J Bacteriol 195(14):3269–3276.  https://doi.org/10.1128/JB.00180-13CrossRefPubMedPubMedCentralGoogle Scholar
  71. Maurin M, Raoult D (1999) Q fever. Clin Microbiol Rev 12 (4):518–553. PMCID: PMC88923Google Scholar
  72. Maurin M, Benoliel AM, Bongrand P, Raoult D (1992) Phagolysosomal alkalinization and the bactericidal effect of antibiotics: theCoxiella burnetii paradigm. J Infect Dis 166(5):1097–1102 PMID: 1402021CrossRefPubMedGoogle Scholar
  73. McDonough JA, Newton HJ, Klum S, Swiss R, Agaisse H, Roy CR (2013) Host pathways important for Coxiella burnetii infection revealed by genome-wide RNA interference screening. MBio 4(1):e00606–00612.  https://doi.org/10.1128/mBio.00606-12CrossRefPubMedPubMedCentralGoogle Scholar
  74. Millar JA, Beare PA, Moses AS, Martens CA, Heinzen RA, Raghavan R (2017) Whole-genome sequence of Coxiella burnetii nine mile RSA439 (Phase II, Clone 4), a laboratory workhorse strain. Genome Announc 5(23).  https://doi.org/10.1128/genomea.00471-17
  75. Morroy G, Keijmel SP, Delsing CE, Bleijenberg G, Langendam M, Timen A, Bleeker-Rovers CP (2016) Fatigue following acute Q-Fever: a systematic literature review. PLoS ONE 11(5):e0155884.  https://doi.org/10.1371/journal.pone.0155884CrossRefPubMedPubMedCentralGoogle Scholar
  76. Mulye M, Samanta D, Winfree S, Heinzen RA, Gilk SD (2017) Elevated cholesterol in the Coxiella burnetii intracellular niche is bacteriolytic. MBio 8(1): https://doi.org/10.1128/mbio.02313-16CrossRefPubMedPubMedCentralGoogle Scholar
  77. Myers E, Ehrhart EJ, Charles B, Spraker T, Gelatt T, Duncan C (2013) Apoptosis in normal and Coxiella burnetii-infected placentas from Alaskan northern fur seals (Callorhinus ursinus). Vet Pathol 50(4):622–625.  https://doi.org/10.1177/0300985812465323CrossRefPubMedGoogle Scholar
  78. Nagai H, Kubori T (2011) Type IVB secretion systems of Legionella and other gram-negative bacteria. Front Microbiol 2:136.  https://doi.org/10.3389/fmicb.2011.00136CrossRefPubMedPubMedCentralGoogle Scholar
  79. Newton HJ, McDonough JA, Roy CR (2013) Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole. PLoS ONE 8(1):e54566.  https://doi.org/10.1371/journal.pone.0054566CrossRefPubMedPubMedCentralGoogle Scholar
  80. Newton HJ, Kohler LJ, McDonough JA, Temoche-Diaz M, Crabill E, Hartland EL, Roy CR (2014) A screen of Coxiella burnetii mutants reveals important roles for Dot/Icm effectors and host autophagy in vacuole biogenesis. PLoS Pathog 10(7):e1004286.  https://doi.org/10.1371/journal.ppat.1004286CrossRefPubMedPubMedCentralGoogle Scholar
  81. Newton P, Latomanski EA, Newton HJ (2016) Applying fluorescence resonance energy transfer (FRET) to examine effector translocation efficiency by Coxiella burnetii during siRNA silencing. J Vis Exp (113).  https://doi.org/10.3791/54210
  82. Norville IH, Hartley MG, Martinez E, Cantet F, Bonazzi M, Atkins TP (2014) Galleria mellonella as an alternative model of Coxiella burnetii infection. Microbiol 160(Pt 6):1175–1181.  https://doi.org/10.1099/mic.0.077230-0CrossRefGoogle Scholar
  83. Omsland A, Cockrell DC, Howe D, Fischer ER, Virtaneva K, Sturdevant DE, Porcella SF, Heinzen RA (2009) Host cell-free growth of the Q fever bacterium Coxiella burnetii. Proc Natl Acad Sci USA 106(11):4430–4434.  https://doi.org/10.1073/pnas.0812074106CrossRefPubMedPubMedCentralGoogle Scholar
  84. Omsland A, Beare PA, Hill J, Cockrell DC, Howe D, Hansen B, Samuel JE, Heinzen RA (2011) Isolation from animal tissue and genetic transformation of Coxiella burnetii are facilitated by an improved axenic growth medium. Appl Environ Microbiol 77(11):3720–3725.  https://doi.org/10.1128/AEM.02826-10CrossRefPubMedPubMedCentralGoogle Scholar
  85. Pan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR (2008) Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Sci 320(5883):1651–1654.  https://doi.org/10.1126/science.1158160CrossRefGoogle Scholar
  86. Rodriguez-Escudero M, Cid VJ, Molina M, Schulze-Luehrmann J, Lührmann A, Rodriguez-Escudero I (2016) Studying Coxiella burnetii type IV substrates in the yeast Saccharomyces cerevisiae: focus on subcellular localization and protein aggregation. PLoS ONE 11(1):e0148032.  https://doi.org/10.1371/journal.pone.0148032CrossRefPubMedPubMedCentralGoogle Scholar
  87. Salvesen GS, Duckett CS (2002) IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 3(6):401–410.  https://doi.org/10.1038/nrm830CrossRefPubMedGoogle Scholar
  88. Schäfer W, Eckart RA, Schmid B, Cagkoylu H, Hof K, Muller YA, Amin B, Lührmann A (2017) Nuclear trafficking of the anti-apoptotic Coxiella burnetii effector protein AnkG requires binding to p 32 and Importin-alpha1. Cell Microbiol 19(1).  https://doi.org/10.1111/cmi.12634
  89. Schoenlaub L, Cherla R, Zhang Y, Zhang G (2016) Coxiella burnetii avirulent nine mile phase II induces caspase-1-dependent pyroptosis in murine peritoneal B1a B cells. Infect Immun 84(12):3638–3654.  https://doi.org/10.1128/IAI.00694-16CrossRefPubMedPubMedCentralGoogle Scholar
  90. Schulze-Luehrmann J, Eckart RA, Olke M, Saftig P, Liebler-Tenorio E, Lührmann A (2016) LAMP proteins account for the maturation delay during the establishment of the Coxiella burnetii-containing vacuole. Cell Microbiol 18(2):181–194.  https://doi.org/10.1111/cmi.12494CrossRefPubMedGoogle Scholar
  91. Seaman MN, McCaffery JM, Emr SD (1998) A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast. J Cell Biol 142(3):665–681.  https://doi.org/10.1083/jcb.142.3.665CrossRefPubMedPubMedCentralGoogle Scholar
  92. Segal G, Feldman M, Zusman T (2005) The Icm/Dot type-IV secretion systems of Legionella pneumophila and Coxiella burnetii. FEMS Microbiol Rev 29(1):65–81.  https://doi.org/10.1016/j.femsre.2004.07.001CrossRefPubMedPubMedCentralGoogle Scholar
  93. Seshadri R, Paulsen IT, Eisen JA, Read TD, Nelson KE, Nelson WC, Ward NL, Tettelin H, Davidsen TM, Beanan MJ, Deboy RT, Daugherty SC, Brinkac LM, Madupu R, Dodson RJ, Khouri HM, Lee KH, Carty HA, Scanlan D, Heinzen RA, Thompson HA, Samuel JE, Fraser CM, Heidelberg JF (2003) Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc Natl Acad Sci USA 100(9):5455–5460.  https://doi.org/10.1073/pnas.0931379100CrossRefPubMedPubMedCentralGoogle Scholar
  94. Sridharan H, Upton JW (2014) Programmed necrosis in microbial pathogenesis. Trends Microbiol 22(4):199–207.  https://doi.org/10.1016/j.tim.2014.01.005CrossRefPubMedGoogle Scholar
  95. van Schaik EJ, Case ED, Martinez E, Bonazzi M, Samuel JE (2017) The SCID mouse model for identifying virulence determinants in Coxiella burnetii. Front Cell Infect Microbiol 7:25.  https://doi.org/10.3389/fcimb.2017.00025CrossRefPubMedPubMedCentralGoogle Scholar
  96. van Schaik EJ, Chen C, Mertens K, Weber MM, Samuel JE (2013) Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii. Nat Rev Microbiol 11(8):561–573CrossRefPubMedPubMedCentralGoogle Scholar
  97. Vazquez CL, Colombo MI (2010) Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection. Cell Death Differ 17(3):421–438.  https://doi.org/10.1038/cdd.2009.129CrossRefPubMedGoogle Scholar
  98. Voth DE, Heinzen RA (2007) Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii. Cell Microbiol 9(4):829–840.  https://doi.org/10.1111/j.1462-5822.2007.00901.xCrossRefPubMedGoogle Scholar
  99. Voth DE, Heinzen RA (2009) Sustained activation of Akt and Erk1/2 is required for Coxiella burnetii antiapoptotic activity. Infect Immun 77(1):205–213.  https://doi.org/10.1128/IAI.01124-08CrossRefPubMedGoogle Scholar
  100. Voth DE, Howe D, Heinzen RA (2007) Coxiella burnetii inhibits apoptosis in human THP-1 cells and monkey primary alveolar macrophages. Infect Immun 75(9):4263–4271.  https://doi.org/10.1128/IAI.00594-07CrossRefPubMedPubMedCentralGoogle Scholar
  101. Voth DE, Beare PA, Howe D, Sharma UM, Samoilis G, Cockrell DC, Omsland A, Heinzen RA (2011) The Coxiella burnetii cryptic plasmid is enriched in genes encoding type IV secretion system substrates. J Bacteriol 193(7):1493–1503.  https://doi.org/10.1128/JB.01359-10CrossRefPubMedPubMedCentralGoogle Scholar
  102. Wallden K, Rivera-Calzada A, Waksman G (2010) Type IV secretion systems: versatility and diversity in function. Cell Microbiol 12(9):1203–1212.  https://doi.org/10.1111/j.1462-5822.2010.01499.xCrossRefPubMedPubMedCentralGoogle Scholar
  103. Weber MM, Chen C, Rowin K, Mertens K, Galvan G, Zhi H, Dealing CM, Roman VA, Banga S, Tan Y, Luo ZQ, Samuel JE (2013) Identification of Coxiella burnetii type IV secretion substrates required for intracellular replication and Coxiella-containing vacuole formation. J Bacteriol 195(17):3914–3924.  https://doi.org/10.1128/JB.00071-13CrossRefPubMedPubMedCentralGoogle Scholar
  104. Weber MM, Faris R, McLachlan J, Tellez A, Wright WU, Galvan G, Luo ZQ, Samuel JE (2016) Modulation of the host transcriptome by Coxiella burnetii nuclear effector Cbu1314. Microbes Infect 18(5):336–345.  https://doi.org/10.1016/j.micinf.2016.01.003CrossRefPubMedGoogle Scholar
  105. Winchell CG, Graham JG, Kurten RC, Voth DE (2014) Coxiella burnetii type IV secretion-dependent recruitment of macrophage autophagosomes. Infect Immun 82(6):2229–2238.  https://doi.org/10.1128/IAI.01236-13CrossRefPubMedPubMedCentralGoogle Scholar
  106. Yu X, Acehan D, Menetret JF, Booth CR, Ludtke SJ, Riedl SJ, Shi Y, Wang X, Akey CW (2005) A structure of the human apoptosome at 12.8 Å resolution provides insights into this cell death platform. Structure 13:1725–1735CrossRefPubMedGoogle Scholar
  107. Zhang Y, Zhang G, Hendrix LR, Tesh VL, Samuel JE (2012) Coxiella burnetii induces apoptosis during early stage infection via a caspase-independent pathway in human monocytic THP-1 cells. PLoS ONE 7(1):e30841.  https://doi.org/10.1371/journal.pone.0030841CrossRefPubMedPubMedCentralGoogle Scholar
  108. Zusman T, Aloni G, Halperin E, Kotzer H, Degtyar E, Feldman M, Segal G (2007) The response regulator PmrA is a major regulator of the icm/dot type IV secretion system in Legionella pneumophila and Coxiella burnetii. Mol Microbiol 63(5):1508–1523.  https://doi.org/10.1111/j.1365-2958.2007.05604.xCrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Mikrobiologisches Institut—Klinische Mikrobiologie, Immunologie und HygieneUniversitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-NürnbergErlangenGermany
  2. 2.Department of Microbiology and ImmunologyUniversity of Melbourne at the Peter Doherty Institute for Infection and ImmunityMelbourneAustralia
  3. 3.Institut de Recherche En Infectiologie de Montpellier (IRIM), CNRSUMR9004, Université de MontpellierMontpellierFrance

Personalised recommendations