Right on Q: Genetics begin to Unravel Coxiella Burnetii host cell Interactions

References

• Raoult D, Marrie T, Mege J. Natural history and pathophysiology of Q fever. Lancet Infect. Dis. 5, 219 – 226 (2005).
   PubMed Web of Science ®Google Scholar
• Kampschreur LM, Delsing CE, Groenwold RH et al. Chronic Q fever in the Netherlands 5 years after the start of the Q fever epidemic: results from the Dutch chronic Q fever database. J. Clin. Microbiol. 52, 1637 – 1643 (2014).
   PubMed Web of Science ®Google Scholar
• Babudieri C. Q fever: a zoonosis. Adv. Vet. Sci. 5, 81 – 84 (1959).
   Google Scholar
• Angelakis E, Raoult D. Q fever. Vet. Microbiol. 140, 297 – 309 (2010).
   PubMed Web of Science ®Google Scholar
• Hackert VH, Van Der Hoek W, Dukers-Muijrers N et al. Q fever: single-point source outbreak with high attack rates and massive numbers of undetected infections across an entire region. Clin. Infect. Dis. 55, 1591 – 1599 (2012).
   PubMed Web of Science ®Google Scholar
• Palmer NC, Kierstead M, Key DW, Williams JC, Peacock MG, Vellend H. Placentitis and abortion in goats and sheep in Ontario caused by Coxiella burnetii. Can. Vet. J. 24, 60 – 61 (1983).
   PubMed Web of Science ®Google Scholar
• Kersh GJ, Wolfe TM, Fitzpatrick KA et al. Presence of Coxiella burnetii DNA in the environment of the United States, 2006 to 2008. Appl. Environ. Microbiol. 76, 4469 – 4475 (2010).
   PubMed Web of Science ®Google Scholar
• Duron O. The IS1111 insertion sequence used for detection of Coxiella burnetii is widespread in Coxiella-like endosymbionts of ticks. FEMS Microbiol. Lett. 362, fnv132 (2015).
   PubMed Web of Science ®Google Scholar
• Van Asseldonk MA, Prins J, Bergevoet RH. Economic assessment of Q fever in the Netherlands. Prev. Vet. Med. 112, 27 – 34 (2013).
   PubMed Web of Science ®Google Scholar
• Beare PA, Unsworth N, Andoh M et al. Comparative genomics reveal extensive transposon-mediated genomic plasticity and diversity among potential effector proteins within the genus Coxiella. Infect. Immun. 77, 642 – 656 (2009).
   PubMed Web of Science ®Google Scholar
• Pearson T, Hornstra HM, Sahl JW et al. When outgroups fail; phylogenomics of rooting the emerging pathogen. Coxiella burnetii. Syst. Biol. 62, 752 – 762 (2013).
   Google Scholar
• Duron O, Noel V, Mccoy KD et al. The recent evolution of a maternally-inherited endosymbiont of ticks led to the emergence of the Q fever pathogen. Coxiella burnetii. PLoS Pathog. 11, e1004892 (2015).
   PubMed Web of Science ®Google Scholar
• Pallen MJ, Wren BW. Bacterial pathogenomics. Nature 449, 835 – 842 (2007).
   PubMed Web of Science ®Google Scholar
• Bliven KA, Maurelli AT. Antivirulence genes: insights into pathogen evolution through gene loss. Infect. Immun. 80, 4061 – 4070 (2012).
   PubMed Web of Science ®Google Scholar
• Van Schaik EJ, Chen C, Mertens K, Weber MM, Samuel JE. Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii. Nat. Rev. Microbiol. 11, 561 – 573 (2013).
   PubMed Web of Science ®Google Scholar
• Russell-Lodrigue KE, Andoh M, Poels MW et al. Coxiella burnetii isolates cause genogroup-specific virulence in mouse and guinea pig models of acute Q fever. Infect. Immun. 77, 5640 – 5650 (2009).
   PubMed Web of Science ®Google Scholar
• Glazunova O, Roux V, Freylikman O et al. Coxiella burnetii genotyping. Emerg. Infect. Dis. 11, 1211 – 1217 (2005).
   PubMed Web of Science ®Google Scholar
• Hornstra HM, Priestley RA, Georgia SM et al. Rapid typing of Coxiella burnetii. PLoS ONE 6, e26201 (2011).
   PubMed Web of Science ®Google Scholar
• Mahamat A, Edouard S, Demar M et al. Unique clone of Coxiella burnetii causing severe Q fever, French Guiana. Emerg. Infect. Dis. 19, 1102 – 1104 (2013).
   PubMed Web of Science ®Google Scholar
• Pearson T, Hornstra HM, Hilsabeck R et al. High prevalence and two dominant host-specific genotypes of Coxiella burnetii in U.S. milk. BMC Microbiol. 14, 41 (2014).
   PubMed Web of Science ®Google Scholar
• Kersh GJ, Oliver LD, Self JS, Fitzpatrick KA, Massung RF. Virulence of pathogenic Coxiella burnetii strains after growth in the absence of host cells. Vector Borne Zoonotic Dis. 11, 1433 – 1438 (2011).
   PubMed Web of Science ®Google Scholar
• Toman R, Skultety L. Structural study on a lipopolysaccharide from Coxiella burnetii strain Nine Mile in avirulent Phase II. Carbohydr. Res. 283, 175 – 185 (1996).
   PubMed Web of Science ®Google Scholar
• Amano K, Williams JC. Chemical and immunological characterization of lipopolysaccharides from Phase I and Phase II Coxiella burnetii. J. Bacteriol. 160, 994 – 1002 (1984).
   PubMed Web of Science ®Google Scholar
• Ftacek P, Skultety L, Toman R. Phase variation of Coxiella burnetii strain Priscilla: influence of this phenomenon on biochemical features of its lipopolysaccharide. J. Endotoxin. Res. 6, 369 – 376 (2000).
   PubMedGoogle Scholar
• Hackstadt T, Peacock MG, Hitchcock PJ, Cole RL. Lipopolysaccharide variation in Coxiella burnetii: intrastrain heterogeneity in structure and antigenicity. Infect. Immun. 48, 359 – 365 (1985).
   PubMed Web of Science ®Google Scholar
• Beare PA, Samuel JE, Howe D, Virtaneva K, Porcella SF, Heinzen RA. Genetic diversity of the Q fever agent, Coxiella burnetii assessed by microarray-based whole-genome comparisons. J. Bacteriol. 188, 2309 – 2324 (2006).
   PubMed Web of Science ®Google Scholar
• Denison AM, Massung RF, Thompson HA. Analysis of the O-antigen biosynthesis regions of Phase II isolates of Coxiella burnetii. FEMS Microbiol. Lett. 267, 102 – 107 (2007).
   PubMed Web of Science ®Google Scholar
• Kuley R, Smith HE, Frangoulidis D, Smits MA, Jan Roest HI, Bossers A. Cell-free propagation of Coxiella burnetii does not affect its relative virulence. PLoS ONE 10, e0121661 (2015).
   PubMed Web of Science ®Google Scholar
• Beare PA, Howe D, Cockrell DC, Heinzen RA. Efficient method of cloning the obligate intracellular bacterium Coxiella burnetii. Appl. Environ. Microbiol. 73, 4048 – 4054 (2007).
   PubMed Web of Science ®Google Scholar
• Hackstadt T. Biosafety concerns and Coxiella burnetii. Trends Microbiol. 4, 341 – 342 (1996).
   PubMed Web of Science ®Google Scholar
• Howe D, Shannon JG, Winfree S, Dorward DW, Heinzen RA. Coxiella burnetii Phase I and II variants replicate with similar kinetics in degradative phagolysosome-like compartments of human macrophages. Infect. Immun. 78, 3465 – 3474 (2010).
   PubMed Web of Science ®Google Scholar
• Graham JG, Macdonald LJ, Hussain SK, Sharma UM, Kurten RC, Voth DE. Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages. Cell. Microbiol. 15, 1012 – 1025 (2013).
   PubMed Web of Science ®Google Scholar
• Moos A, Hackstadt T. Comparative virulence of intra- and interstrain lipopolysaccharide variants of Coxiella burnetii in the guinea pig model. Infect. Immun. 55, 1144 – 1150 (1987).
   PubMed Web of Science ®Google Scholar
• Williams JC, Peacock MG, Mccaul TF. Immunological and biological characterization of Coxiella burnetii Phases I and II, separated from host components. Infect. Immun. 32, 840 – 851 (1981).
   PubMed Web of Science ®Google Scholar
• Hackstadt T. Steric hindrance of antibody binding to surface proteins of Coxiella burnetti by Phase I lipopolysaccharide. Infect. Immun. 56, 802 – 807 (1988).
   PubMed Web of Science ®Google Scholar
• Zamboni DS, Campos MA, Torrecilhas AC et al. Stimulation of toll-like receptor 2 by Coxiella burnetii is required for macrophage production of pro-inflammatory cytokines and resistance to infection. J. Biol. Chem. 279, 54405 – 54415 (2004).
   PubMed Web of Science ®Google Scholar
• Bradley WP, Boyer MA, Nguyen HT et al. Primary role for TLR-driven TNF rather than cytosolic immune detection in restricting Coxiella burnetii Phase II replication within mouse macrophages. Infect. Immun. 84, 998 – 1015 (2016).
   PubMed Web of Science ®Google Scholar
• Zamboni DS, Rabinovitch M. Phagocytosis of apoptotic cells increases the susceptibility of macrophages to infection with Coxiella burnetii Phase II through down-modulation of nitric oxide production. Infect. Immun. 72, 2075 – 2080 (2004).
   PubMed Web of Science ®Google Scholar
• Zamboni DS. Genetic control of natural resistance of mouse macrophages to Coxiella burnetii infection in vitro: macrophages from restrictive strains control parasitophorous vacuole maturation. Infect. Immun. 72, 2395 – 2399 (2004).
   PubMed Web of Science ®Google Scholar
• Shannon JG, Howe D, Heinzen RA. Virulent Coxiella burnetii does not activate human dendritic cells: role of lipopolysaccharide as a shielding molecule. Proc. Natl Acad. Sci. USA 102, 8722 – 8727 (2005).
   PubMed Web of Science ®Google Scholar
• Khavkin T, Tabibzadeh SS. Histologic, immunofluorescence, and electron microscopic study of infectious process in mouse lung after intranasal challenge with Coxiella burnetii. Infect. Immun. 56, 1792 – 1799 (1988).
   PubMed Web of Science ®Google Scholar
• Graham JG, Winchell CG, Kurten RC, Voth DE. Development of an ex vivo tissue platform to study the human lung response to Coxiella burnetii. Infect. Immun. 84 (5 ), 1438 – 1445 (2016).
   PubMed Web of Science ®Google Scholar
• Calverley M, Erickson S, Read AJ, Harmsen AG. Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection. PLoS ONE 7, e51941 (2012).
   PubMed Web of Science ®Google Scholar
• Stein A, Louveau C, Lepidi H et al. Q fever pneumonia: virulence of Coxiella burnetii pathovars in a murine model of aerosol infection. Infect. Immun. 73, 2469 – 2477 (2005).
   PubMed Web of Science ®Google Scholar
• Sanchez J, Souriau A, Buendia AJ et al. Experimental Coxiella burnetii infection in pregnant goats: a histopathological and immunohistochemical study. J. Comp. Pathol. 135, 108 – 115 (2006).
   PubMed Web of Science ®Google Scholar
• Bechah Y, Verneau J, Ben Amara A et al. Persistence of Coxiella burnetii the agent of Q fever, in murine adipose tissue. PLoS ONE 9, e97503 (2014).
   PubMed Web of Science ®Google Scholar
• Voth DE, Heinzen RA. Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii. Cell. Microbiol. 9, 829 – 840 (2007).
   PubMed Web of Science ®Google Scholar
• Baca OG, Klassen DA, Aragon AS. Entry of Coxiella burnetii into host cells. Acta Virol. 37, 143 – 155 (1993).
   PubMed Web of Science ®Google Scholar
• Tujulin E, Macellaro A, Lilliehook B, Norlander L. Effect of endocytosis inhibitors on Coxiella burnetii interaction with host cells. Acta Virol. 42, 125 – 131 (1998).
   PubMed Web of Science ®Google Scholar
• Martinez E, Cantet F, Fava L, Norville I, Bonazzi M. Identification of OmpA, a Coxiella burnetii protein involved in host cell invasion, by multi-phenotypic high-content screening. PLoS Pathog. 10, e1004013 (2014).
   PubMed Web of Science ®Google Scholar
• Capo C, Lindberg FP, Meconi S et al. Subversion of monocyte functions by Coxiella burnetii: impairment of the cross-talk between avb3 integrin and CR3. J. Immunol. 163, 6078 – 6085 (1999).
   PubMed Web of Science ®Google Scholar
• Meconi S, Jacomo V, Boquet P, Raoult D, Mege JL, Capo C. Coxiella burnetii induces reorganization of the actin cytoskeleton in human monocytes. Infect. Immun. 66, 5527 – 5533 (1998).
   PubMed Web of Science ®Google Scholar
• Salinas RP, Ortiz Flores RM, Distel JS, Aguilera MO, Colombo MI, Beron W. Coxiella burnetii phagocytosis Is regulated by GTPases of the Rho family and the RhoA effectors mDia1 and ROCK. PLoS ONE 10, e0145211 (2015).
   PubMed Web of Science ®Google Scholar
• Meconi S, Capo C, Remacle-Bonnet M, Pommier G, Raoult D, Mege JL. Activation of protein tyrosine kinases by Coxiella burnetii: role in actin cytoskeleton reorganization and bacterial phagocytosis. Infect. Immun. 69, 2520 – 2526 (2001).
   PubMed Web of Science ®Google Scholar
• Rosales EM, Aguilera MO, Salinas RP et al. Cortactin is involved in the entry of Coxiella burnetii into nonphagocytic cells. PLoS ONE 7, e39348 (2012).
   PubMed Web of Science ®Google Scholar
• Romano PS, Gutierrez MG, Beron W, Rabinovitch M, Colombo MI. The autophagic pathway is actively modulated by Phase II Coxiella burnetii to efficiently replicate in the host cell. Cell. Microbiol. 9, 891 – 909 (2007).
   PubMed Web of Science ®Google Scholar
• Schulze-Luehrmann J, Eckart RA, Olke M, Saftig P, Liebler-Tenorio E, Luhrmann A. LAMP proteins account for the maturation delay during the establishment of the Coxiella burnetii-containing vacuole. Cell. Microbiol. 18, 181 – 194 (2016).
   PubMed Web of Science ®Google Scholar
• Aguilera M, Salinas R, Rosales E, Carminati S, Colombo MI, Beron W. Actin dynamics and Rho GTPases regulate the size and formation of parasitophorous vacuoles containing Coxiella burnetii. Infect. Immun. 77, 4609 – 4620 (2009).
   PubMed Web of Science ®Google Scholar
• Vazquez CL, Colombo MI. Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection. Cell. Death Differ. 17, 421 – 438 (2010).
   PubMed Web of Science ®Google Scholar
• Newton HJ, Kohler LJ, Mcdonough JA et al. A screen of Coxiella burnetii mutants reveals important roles for Dot/Icm effectors and host autophagy in vacuole biogenesis. PLoS Pathog. 10, e1004286 (2014).
   PubMed Web of Science ®Google Scholar
• Flannagan RS, Cosio G, Grinstein S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat. Rev. Microbiol. 7, 355 – 366 (2009).
   PubMed Web of Science ®Google Scholar
• Case ED, Smith JA, Ficht TA, Samuel JE, De Figueiredo P. Space: a final frontier for vacuolar pathogens. Traffic 17, 461 – 474 (2016).
   PubMed Web of Science ®Google Scholar
• Voth DE, Howe D, Heinzen RA. Coxiella burnetii inhibits apoptosis in human THP-1 cells and monkey primary alveolar macrophages. Infect. Immun. 75, 4263 – 4271 (2007).
   PubMed Web of Science ®Google Scholar
• Hackstadt T, Williams JC. Incorporation of macromolecular precursors by Coxiella burnetii in an axenic medium. In : Rickettsiae and Rickettsial Diseases. Burgdorfer W, Anacker RL( Eds ) . Academic Press, Inc., NY, USA, 431 – 440 (1981).
   Google Scholar
• Howe D, Melnicakova J, Barak I, Heinzen RA. Maturation of the Coxiella burnetii parasitophorous vacuole requires bacterial protein synthesis but not replication. Cell Microbiol. 5, 469 – 480 (2003).
   PubMed Web of Science ®Google Scholar
• Deretic V, Levine B. Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5, 527 – 549 (2009).
   PubMed Web of Science ®Google Scholar
• Winchell CG, Graham JG, Kurten RC, Voth DE. Coxiella burnetii type IV secretion-dependent recruitment of macrophage autophagosomes. Infect. Immun. 82, 2229 – 2238 (2014).
   PubMed Web of Science ®Google Scholar
• Beron W, Gutierrez MG, Rabinovitch M, Colombo MI. Coxiella burnetii localizes in a Rab7-labeled compartment with autophagic characteristics. Infect. Immun. 70, 5816 – 5821 (2002).
   PubMed Web of Science ®Google Scholar
• Campoy EM, Zoppino FC, Colombo MI. The early secretory pathway contributes to the growth of the Coxiella-replicative niche. Infect. Immun. 79, 402 – 413 (2011).
   PubMed Web of Science ®Google Scholar
• Gutierrez MG, Vazquez CL, Munafo DB et al. Autophagy induction favours the generation and maturation of the Coxiella-replicative vacuoles. Cell. Microbiol. 7, 981 – 993 (2005).
   PubMed Web of Science ®Google Scholar
• Kohler LJ, Roy CR. Biogenesis of the lysosome-derived vacuole containing Coxiella burnetii. Microbes Infect. 17, 766 – 771 (2015).
   PubMed Web of Science ®Google Scholar
• Mcdonough JA, Newton HJ, Klum S, Swiss R, Agaisse H, Roy CR. Host pathways important for Coxiella burnetii infection revealed by genome-wide RNA interference screening. MBio 4, e00606 – e00612 (2013).
   PubMed Web of Science ®Google Scholar
• Larson CL, Beare PA, Howe D, Heinzen RA. Coxiella burnetii effector protein subverts clathrin-mediated vesicular trafficking for pathogen vacuole biogenesis. Proc. Natl Acad. Sci. USA 110, E4770 – E4779 (2013).
   PubMed Web of Science ®Google Scholar
• Itakura E, Mizushima N. Syntaxin 17: the autophagosomal SNARE. Autophagy 9, 917 – 919 (2013).
   PubMed Web of Science ®Google Scholar
• Campoy EM, Mansilla ME, Colombo MI. Endocytic SNAREs are involved in optimal Coxiella burnetii vacuole development. Cell. Microbiol. 15, 922 – 941 (2013).
   PubMed Web of Science ®Google Scholar
• Coleman SA, Fischer ER, Howe D, Mead DJ, Heinzen RA. Temporal analysis of Coxiella burnetii morphological differentiation. J. Bacteriol. 186, 7344 – 7352 (2004).
   PubMed Web of Science ®Google Scholar
• Luhrmann A, Roy CR. Coxiella burnetii inhibits activation of host cell apoptosis through a mechanism that involves preventing cytochrome c release from mitochondria. Infect. Immun. 75, 5282 – 5289 (2007).
   PubMed Web of Science ®Google Scholar
• Voth DE, Heinzen RA. Sustained activation of Akt and Erk1/2 is required for Coxiella burnetii antiapoptotic activity. Infect. Immun. 77, 205 – 213 (2009).
   PubMed Web of Science ®Google Scholar
• Macdonald LJ, Graham JG, Kurten RC, Voth DE. Coxiella burnetii exploits host cAMP-dependent protein kinase signalling to promote macrophage survival. Cell Microbiol. 16, 146 – 159 (2014).
   PubMed Web of Science ®Google Scholar
• Beare PA, Gilk SD, Larson CL et al. Dot/Icm type IVB secretion system requirements for Coxiella burnetii growth in human macrophages. MBio 2, e00175–00111 (2011).
   Web of Science ®Google Scholar
• Macdonald LJ, Kurten RC, Voth DE. Coxiella burnetii alters cyclic AMP-dependent protein kinase signaling during growth in macrophages. Infect. Immun. 80, 1980 – 1986 (2012).
   PubMed Web of Science ®Google Scholar
• Seshadri R, Paulsen IT, Eisen JA et al. Complete genome sequence of the Q-fever pathogen Coxiella burnetii. Proc. Natl Acad. Sci. USA 100, 5455 – 5460 (2003).
   PubMed Web of Science ®Google Scholar
• Segal G, Shuman HA. Possible origin of the Legionella pneumophila virulence genes and their relation to Coxiella burnetii. Mol. Microbiol. 33, 669 – 670 (1999).
   PubMed Web of Science ®Google Scholar
• Segal G, Feldman M, Zusman T. The Icm/Dot type-IV secretion systems of Legionella pneumophila and Coxiella burnetii. FEMS Microbiol. Rev. 29, 65 – 81 (2005).
   PubMed Web of Science ®Google Scholar
• Zusman T, Yerushalmi G, Segal G. Functional similarities between the icm/dot pathogenesis systems of Coxiella burnetii and Legionella pneumophila. Infect. Immun. 71, 3714 – 3723 (2003).
   PubMed Web of Science ®Google Scholar
• Zamboni DS, Mcgrath S, Rabinovitch M, Roy CR. Coxiella burnetii express type IV secretion system proteins that function similarly to components of the Legionella pneumophila Dot/Icm system. Mol. Microbiol. 49, 965 – 976 (2003).
   PubMed Web of Science ®Google Scholar
• Carey KL, Newton HJ, Luhrmann A, Roy CR. 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, e1002056 (2011).
   PubMed Web of Science ®Google Scholar
• Chen C, Banga S, Mertens K et al. Large-scale identification and translocation of type IV secretion substrates by Coxiella burnetii. Proc. Natl Acad. Sci. USA 107, 21755 – 21760 (2010).
   PubMed Web of Science ®Google Scholar
• Lifshitz Z, Burstein D, Peeri M et al. Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal. Proc. Natl Acad. Sci. USA 110, 707 – 715 (2013).
   PubMed Web of Science ®Google Scholar
• Pan X, Luhrmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science 320, 1651 – 1654 (2008).
   PubMed Web of Science ®Google Scholar
• Voth DE, Beare PA, Howe D et al. The Coxiella burnetii cryptic plasmid is enriched in genes encoding type IV secretion system substrates. J. Bacteriol. 193, 1493 – 1503 (2011).
   PubMed Web of Science ®Google Scholar
• Voth DE, Howe D, Beare PA et al. The Coxiella burnetii ankyrin repeat domain-containing protein family is heterogeneous, with C-terminal truncations that influence Dot/Icm-mediated secretion. J. Bacteriol. 191, 4232 – 4242 (2009).
   PubMed Web of Science ®Google Scholar
• Maturana P, Graham JG, Sharma UM, Voth DE. Refining the plasmid-encoded type IV secretion system substrate repertoire of Coxiella burnetii. J. Bacteriol. 195, 3269 – 3276 (2013).
   PubMed Web of Science ®Google Scholar
• Weber MM, Chen C, Rowin K et al. Identification of Coxiella burnetii type IV secretion substrates required for intracellular replication and Coxiella-containing vacuole formation. J. Bacteriol. 195, 3914 – 3924 (2013).
   PubMed Web of Science ®Google Scholar
• Lifshitz Z, Burstein D, Schwartz K, Shuman HA, Pupko T, Segal G. Identification of novel Coxiella burnetii Icm/Dot effectors and genetic analysis of their involvement in modulating a mitogen-activated protein kinase pathway. Infect. Immun. 82, 3740 – 3752 (2014).
   PubMed Web of Science ®Google Scholar
• Graham JG, Winchell CG, Sharma UM, Voth DE. Identification of ElpA, a Coxiella burnetii pathotype-specific Dot/Icm type IV secretion system substrate. Infect. Immun. 83, 1190 – 1198 (2015).
   PubMed Web of Science ®Google Scholar
• Luhrmann A, Nogueira CV, Carey KL, Roy CR. Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein. Proc. Natl Acad. Sci. USA 107, 18997 – 19001 (2010).
   PubMed Web of Science ®Google Scholar
• Cunha LD, Ribeiro JM, Fernandes TD et al. Inhibition of inflammasome activation by Coxiella burnetii type IV secretion system effector IcaA. Nat. Commun. 6, 10205 (2015).
   PubMed Web of Science ®Google Scholar
• Falkow S. Molecular Koch's postulates applied to bacterial pathogenicity – a personal recollection 15 years later. Nat. Rev. Microbiol. 2, 67 – 72 (2004).
   PubMed Web of Science ®Google Scholar
• Beare PA, Sandoz KM, Omsland A, Rockey DD, Heinzen RA. Advances in genetic manipulation of obligate intracellular bacterial pathogens. Front. Microbiol. 2, 97 (2011).
   PubMed Web of Science ®Google Scholar
• Beare PA, Howe D, Cockrell DC, Omsland A, Hansen B, Heinzen RA. Characterization of a Coxiella burnetii ftsZ mutant generated by Himar1 transposon mutagenesis. J. Bacteriol. 191, 1369 – 1381 (2009).
   PubMed Web of Science ®Google Scholar
• Omsland A, Cockrell DC, Howe D et al. Host cell-free growth of the Q fever bacterium Coxiella burnetii. Proc. Natl Acad. Sci. USA 106, 4430 – 4434 (2009).
   PubMed Web of Science ®Google Scholar
• Omsland A, Beare PA, Hill J et al. Isolation from animal tissue and genetic transformation of Coxiella burnetii are facilitated by an improved axenic growth medium. Appl. Environ. Microbiol. 77, 3720 – 3725 (2011).
   PubMed Web of Science ®Google Scholar
• Beare PA, Larson CL, Gilk SD, Heinzen RA. Two systems for targeted gene deletion in Coxiella burnetii. Appl. Environ. Microbiol. 78, 4580 – 4589 (2012).
   PubMed Web of Science ®Google Scholar
• Beare PA, Sandoz KM, Larson CL, Howe D, Kronmiller B, Heinzen RA. Essential role for the response regulator PmrA in Coxiella burnetii type 4B secretion and colonization of mammalian host cells. J. Bacteriol. 196, 1925 – 1940 (2014).
   PubMed Web of Science ®Google Scholar
• Sandoz KM, Beare PA, Cockrell DC, Heinzen RA. A defined axenic medium allows complementation of arginine auxotrophy for genetic transformation of Coxiella burnetii. Appl. Environ. Microbiol. 82, 3042 – 3051 (2016).
   PubMed Web of Science ®Google Scholar
• Larson CL, Beare PA, Voth DE et al. Coxiella burnetii effector proteins that localize to the parasitophorous vacuole membrane promote intracellular replication. Infect. Immun. 83, 661 – 670 (2015).
   PubMed Web of Science ®Google Scholar
• Newton HJ, Mcdonough JA, Roy CR. Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole. PLoS ONE 8, e54566 (2013).
   PubMed Web of Science ®Google Scholar
• Kubori T, Hyakutake A, Nagai H. Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol. Microbiol. 67, 1307 – 1319 (2008).
   PubMed Web of Science ®Google Scholar
• Nagai H, Cambronne ED, Kagan JC, Amor JC, Kahn RA, Roy CR. A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells. Proc. Natl Acad. Sci. USA 102, 826 – 831 (2005).
   PubMed Web of Science ®Google Scholar
• Burstein D, Zusman T, Degtyar E, Viner R, Segal G, Pupko T. Genome-scale identification of Legionella pneumophila effectors using a machine learning approach. PLoS Pathog. 5, e1000508 (2009).
   PubMed Web of Science ®Google Scholar
• Huang L, Boyd D, Amyot WM et al. The E Block motif is associated with Legionella pneumophila translocated substrates. Cell Microbiol. 13, 227 – 245 (2011).
   PubMed Web of Science ®Google Scholar
• De Felipe KS, Pampou S, Jovanovic OS et al. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 187, 7716 – 7726 (2005).
   PubMed Web of Science ®Google Scholar
• Zusman T, Aloni G, Halperin E et al. 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, 1508 – 1523 (2007).
   PubMed Web of Science ®Google Scholar
• Segal G. The Legionella pneumophila two-component regulatory systems that participate in the regulation of Icm/Dot effectors. Curr. Top. Microbiol. Immunol. 376, 35 – 52 (2013).
   PubMed Web of Science ®Google Scholar
• Sutherland MC, Binder KA, Cualing PY, Vogel JP. Reassessing the role of DotF in the Legionella pneumophila type IV secretion system. PLoS ONE 8, e65529 (2013).
   PubMed Web of Science ®Google Scholar
• Luo ZQ, Isberg RR. Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer. Proc. Natl Acad. Sci. USA 101, 841 – 846 (2004).
   PubMed Web of Science ®Google Scholar
• Waag DM, Byrne WR, Estep J, Gibbs P, Pitt ML, Banfield CM. Evaluation of cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) monkeys as experimental models of acute Q fever after aerosol exposure to Phase-I Coxiella burnetii. Lab. Anim. Sci. 49, 634 – 638 (1999).
   PubMedGoogle Scholar
• Jeong KC, Sutherland MC, Vogel JP. Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences. Mol. Microbiol. 96, 175 – 188 (2015).
   PubMed Web of Science ®Google Scholar
• Schnell U, Dijk F, Sjollema KA, Giepmans BN. Immunolabeling artifacts and the need for live-cell imaging. Nat. Methods 9, 152 – 158 (2012).
   PubMed Web of Science ®Google Scholar
• Eckart RA, Bisle S, Schulze-Luehrmann J et al. Antiapoptotic activity of Coxiella burnetii effector protein AnkG is controlled by p32-dependent trafficking. Infect. Immun. 82, 2763 – 2771 (2014).
   PubMed Web of Science ®Google Scholar
• Rodriguez-Escudero M, Cid VJ, Molina M, Schulze-Luehrmann J, Luhrmann A, Rodriguez-Escudero I. Studying Coxiella burnetii type IV substrates in the yeast Saccharomyces cerevisiae: focus on subcellular localization and protein aggregation. PLoS ONE 11, e0148032 (2016).
   PubMed Web of Science ®Google Scholar
• Weber MM, Faris R, Mclachlan J et al. Modulation of the host transcriptome by Coxiella burnetii nuclear effector Cbu1314. Microbes Infect. 18 (5 ), 336 – 345 (2016).
   PubMed Web of Science ®Google Scholar
• Siggers KA, Lesser CF. The yeast Saccharomyces cerevisiae: a versatile model system for the identification and characterization of bacterial virulence proteins. Cell Host Microbe 4, 8 – 15 (2008).
   PubMed Web of Science ®Google Scholar
• Ashida H, Mimuro H, Ogawa M et al. Cell death and infection: a double-edged sword for host and pathogen survival. J. Cell Biol. 195, 931 – 942 (2011).
   PubMed Web of Science ®Google Scholar
• Klingenbeck L, Eckart RA, Berens C, Luhrmann A. The Coxiella burnetii type IV secretion system substrate CaeB inhibits intrinsic apoptosis at the mitochondrial level. Cell Microbiol. 15, 675 – 687 (2013).
   PubMed Web of Science ®Google Scholar
• Bisle S, Klingenbeck L, Borges V et al. 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 (2016).
   PubMed Web of Science ®Google Scholar
• Bonifacino JS, Traub LM. Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu. Rev. Biochem. 72, 395 – 447 (2003).
   PubMed Web of Science ®Google Scholar
• Keyel PA, Mishra SK, Roth R, Heuser JE, Watkins SC, Traub LM. A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Mol. Biol. Cell 17, 4300 – 4317 (2006).
   PubMed Web of Science ®Google Scholar
• Motley A, Bright NA, Seaman MN, Robinson MS. Clathrin-mediated endocytosis in AP-2-depleted cells. J. Cell Biol. 162, 909 – 918 (2003).
   PubMed Web of Science ®Google Scholar
• Martinez E, Allombert J, Cantet F et al. The Coxiella burnetii effector CvpB modulates phosphoinositide metabolism for optimal vacuole development. Proc. Natl Acad. Sci. USA 113, E3260 – E3269 (2016).
   PubMed Web of Science ®Google Scholar
• 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 108, 14733 – 14740 (2011).
   PubMed Web of Science ®Google Scholar
• Brodin P, Christophe T. High-content screening in infectious diseases. Curr. Opin. Chem. Biol. 15, 534 – 539 (2011).
   PubMed Web of Science ®Google Scholar
• Boutros M, Heigwer F, Laufer C. Microscopy-based high-content screening. Cell 163, 1314 – 1325 (2015).
   PubMed Web of Science ®Google Scholar
• Selvaraj SK, Prasadarao NV. Escherichia coli K1 inhibits proinflammatory cytokine induction in monocytes by preventing NF-kappaB activation. J. Leukoc. Biol. 78, 544 – 554 (2005).
   PubMed Web of Science ®Google Scholar
• Stead CM, Omsland A, Beare PA, Sandoz KM, Heinzen RA. Sec-mediated secretion by Coxiella burnetii. BMC Microbiol. 13, 222 (2013).
   PubMed Web of Science ®Google Scholar
• Charpentier X, Gabay JE, Reyes M, Zhu JW, Weiss A, Shuman HA. Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila. PLoS Pathog. 5, e1000501 (2009).
   PubMed Web of Science ®Google Scholar
• Roy CR, Berger KH, Isberg RR. Legionella pneumophila DotA protein is required for early phagosome trafficking decisions that occur within minutes of bacterial uptake. Mol. Microbiol. 28, 663 – 674 (1998).
   PubMed Web of Science ®Google Scholar
• Yu XJ, Mcgourty K, Liu M, Unsworth KE, Holden DW. pH sensing by intracellular Salmonella induces effector translocation. Science 328, 1040 – 1043 (2010).
   PubMed Web of Science ®Google Scholar
• Deng W, Li Y, Hardwidge PR et al. Regulation of type III secretion hierarchy of translocators and effectors in attaching and effacing bacterial pathogens. Infect. Immun. 73, 2135 – 2146 (2005).
   PubMed Web of Science ®Google Scholar
• Cambronne ED, Roy CR. The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation. PLoS Pathog. 3, e188 (2007).
   PubMed Web of Science ®Google Scholar
• Sutherland MC, Nguyen TL, Tseng V, Vogel JP. The Legionella IcmSW complex directly interacts with DotL to mediate translocation of adaptor-dependent substrates. PLoS Pathog. 8, e1002910 (2012).
   PubMed Web of Science ®Google Scholar
• Baca OG, Scott TO, Akporiaye ET, Deblassie R, Crissman HA. Cell cycle distribution patterns and generation times of L929 fibroblast cells persistently infected with Coxiella burnetii. Infect. Immun. 47, 366 – 369 (1985).
   PubMed Web of Science ®Google Scholar
• Barquist L, Boinett CJ, Cain AK. Approaches to querying bacterial genomes with transposon-insertion sequencing. RNA Biol. 10, 1161 – 1169 (2013).
   PubMed Web of Science ®Google Scholar
• Wright AV, Nunez JK, Doudna JA. Biology and applications of CRISPR systems: harnessing nature's toolbox for genome engineering. Cell 164, 29 – 44 (2016).
   PubMed Web of Science ®Google Scholar
• Michard C, Sperandio D, Bailo N et al. The Legionella kinase LegK2 targets the ARP2/3 complex to inhibit actin nucleation on phagosomes and allow bacterial evasion of the late endocytic pathway. MBio 6, e00354 – e00315 (2015).
   PubMed Web of Science ®Google Scholar
• Zhou Y, Zhu Y. Diversity of bacterial manipulation of the host ubiquitin pathways. Cell. Microbiol. 17, 26 – 34 (2015).
   PubMed Web of Science ®Google Scholar
• Rolando M, Sanulli S, Rusniok C et al. Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication. Cell Host Microbe 13, 395 – 405 (2013).
   PubMed Web of Science ®Google Scholar
• Bierne H, Cossart P. When bacteria target the nucleus: the emerging family of nucleomodulins. Cell. Microbiol. 14, 622 – 633 (2012).
   PubMed Web of Science ®Google Scholar
• Ensminger AW. Legionella pneumophila armed to the hilt: justifying the largest arsenal of effectors in the bacterial world. Curr. Opin. Microbiol. 29, 74 – 80 (2015).
   PubMed Web of Science ®Google Scholar
• Jeong KC, Sexton JA, Vogel JP. Spatiotemporal regulation of a Legionella pneumophila T4SS substrate by the metaeffector SidJ. PLoS Pathog. 11, e1004695 (2015).
   PubMed Web of Science ®Google Scholar
• Andoh M, Zhang G, Russell-Lodrigue KE, Shive HR, Weeks BR, Samuel JE. T cells are essential for bacterial clearance, and gamma interferon, tumor necrosis factor alpha, and B cells are crucial for disease development in Coxiella burnetii infection in mice. Infect. Immun. 75, 3245 – 3255 (2007).
   PubMed Web of Science ®Google Scholar
• Islam A, Lockhart M, Stenos J, Graves S. The attenuated Nine Mile Phase II clone 4/RSA439 strain of Coxiella burnetii is highly virulent for severe combined immunodeficient (SCID) mice. Am. J. Trop. Med. Hyg. 89, 800 – 803 (2013).
   PubMed Web of Science ®Google Scholar
• Ochoa-Reparaz J, Sentissi J, Trunkle T, Riccardi C, Pascual DW. Attenuated Coxiella burnetii Phase II causes a febrile response in gamma interferon knockout and Toll-like receptor 2 knockout mice and protects against reinfection. Infect. Immun. 75, 5845 – 5858 (2007).
   PubMed Web of Science ®Google Scholar
• Norville IH, Hartley MG, Martinez E, Cantet F, Bonazzi M, Atkins TP. Galleria mellonella as an alternative model of Coxiella burnetii infection. Microbiology 160, 1175 – 1181 (2014).
   PubMed Web of Science ®Google Scholar