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.
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References
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: PMC348171
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.00023-09
Angelakis E, Raoult D (2010) Q Fever Vet Microbiol 140(3–4):297–309. https://doi.org/10.1016/j.vetmic.2009.07.016
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.2006.02.008
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.00218-17
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/10.1177/1753425916679255
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.01580-08
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.00175-11
Benenson AS, Tigertt WD (1956) Studies on Q fever in man. Trans Assoc Am Physicians 69:98–104 PMID: 13380951
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/nrmicro2070
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.70.10.5816-5821.2002
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/10.1080/21505594.2016.1139280
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.01536-15
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/10.1186/1471-2334-13-488
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: 4100953
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: PMC422031
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.1002056
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-062911-102821
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.1010485107
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.186.21.7344-7352.2004
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/nrc883
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/ncomms10205
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.01534-14
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: PMC101522
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_12
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.01204-13
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/10.1038/34112
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.01046-16
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-011811-132445
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.2017.03.001
Gallon M, Cullen PJ (2015) Retromer and sorting nexins in endosomal sorting. Biochem Soc Trans 43(1):33–47. https://doi.org/10.1042/BST20140290
Gallucci S, Lolkema M, Matzinger P (1999) Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5(11):1249–1255. https://doi.org/10.1038/15200
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.201643598
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_10
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.1003107
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.12096
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.00012-16
Green DR, Llambi F (2015) Cell death signaling. Cold Spring Harb Perspect Biol 7(12). https://doi.org/10.1101/cshperspect.a006080
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.13896
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.x
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: PMC319537
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/nature11910
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.00510-12
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: PMC173840
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.1355.020
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.x
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.00406-10
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.2012.11.001
Jorgensen I, Miao EA (2015) Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 265(1):130–142. https://doi.org/10.1111/imr.12287
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.12637
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/nrm4024
Kersh GJ (2013) Antimicrobial therapies for Q fever. Expert Rev Anti Infect Ther 11(11):1207–1214. https://doi.org/10.1586/14787210.2013.840534
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.12066
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.01127-16
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.2010.06.007
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.1309195110
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-2016-0044
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.1006101
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.00863-07
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.1004380107
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-y
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.12213
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: 14592601
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.7601689
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.12534
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.2017.00112
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),91469-5
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.1004013
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.1522811113
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.00180-13
Maurin M, Raoult D (1999) Q fever. Clin Microbiol Rev 12 (4):518–553. PMCID: PMC88923
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: 1402021
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.00606-12
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
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.0155884
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.02313-16
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/10.1177/0300985812465323
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.2011.00136
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.0054566
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.1004286
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
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.0.077230-0
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.0812074106
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.02826-10
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.1158160
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.0148032
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/nrm830
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
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.00694-16
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.12494
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.142.3.665
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.2004.07.001
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.0931379100
Sridharan H, Upton JW (2014) Programmed necrosis in microbial pathogenesis. Trends Microbiol 22(4):199–207. https://doi.org/10.1016/j.tim.2014.01.005
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.2017.00025
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):561–573
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.2009.129
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.x
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.01124-08
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.00594-07
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.01359-10
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.x
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.00071-13
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.2016.01.003
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.01236-13
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 13:1725–1735
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.0030841
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.x
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Lührmann, A., Newton, H.J., Bonazzi, M. (2017). Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis. In: Backert, S., Grohmann, E. (eds) Type IV Secretion in Gram-Negative and Gram-Positive Bacteria. Current Topics in Microbiology and Immunology, vol 413. Springer, Cham. https://doi.org/10.1007/978-3-319-75241-9_10
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