1887

Abstract

is a Gram-negative obligate intracellular pathogen and the causative agent of Q fever in humans. Q fever causes acute flu-like symptoms and may develop into a chronic disease leading to endocarditis. Its potential as a bioweapon has led to its classification as a category B select agent. An effective inactivated whole-cell vaccine (WCV) currently exists but causes severe granulomatous/necrotizing reactions in individuals with prior exposure, and is not licensed for use in most countries. Current efforts to reduce or eliminate the deleterious reactions associated with WCVs have focused on identifying potential subunit vaccine candidates. Both humoral and T cell-mediated responses are required for protection in animal models. In this study, nine novel immunogenic proteins were identified in extracted whole-cell lysates using 2D electrophoresis, immunoblotting with immune guinea pig sera, and tandem MS. The immunogenic proteins elicited antigen-specific IgG in guinea pigs vaccinated with whole-cell killed Nine Mile phase I vaccine, suggesting a T cell-dependent response. Eleven additional proteins previously shown to react with immune human sera were also antigenic in guinea pigs, showing the relevance of the guinea pig immunization model for antigen discovery. The antigens described here warrant further investigation to validate their potential use as subunit vaccine candidates.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.043513-0
2011-02-01
2020-10-01
Loading full text...

Full text loading...

/deliver/fulltext/micro/157/2/526.html?itemId=/content/journal/micro/10.1099/mic.0.043513-0&mimeType=html&fmt=ahah

References

  1. Andoh M., Naganawa T., Hotta A., Yamaguchi T., Fukushi H., Masegi T., Hirai K.. 2003; SCID mouse model for lethal Q fever. Infect Immun71:4717–4723
    [Google Scholar]
  2. Andoh M., Zhang G., Russell-Lodrigue K. E., Shive H. R., Weeks B. R., Samuel J. E.. 2007; T cells are essential for bacterial clearance, and gamma interferon, tumor necrosis factor alpha, and B cells are critical for disease development in Coxiella burnetii infection in mice. Infect Immun75:3245–3255
    [Google Scholar]
  3. Arricau Bouvery N., Souriau A., Lechopier P., Rodolakis A.. 2003; Experimental Coxiella burnetii infection in pregnant goats: excretion routes. Vet Res34:423–433
    [Google Scholar]
  4. Ascher M. S., Williams J. C., Berman M. A.. 1983; Dermal granulomatous hypersensitivity in Q fever: comparative studies of the granulomatous potential of whole cells of Coxiella burnetii phase I and subfractions. Infect Immun42:887–889
    [Google Scholar]
  5. Baca O. G.. 1978; Comparison of ribosomes from Coxiella burnetii and Escherichia coli by gel electrophoresis, protein synthesis, and immunological techniques. J Bacteriol136:429–432
    [Google Scholar]
  6. Balasubramanian S., Kannan T. R., Baseman J. B.. 2008; The surface-exposed carboxyl region of Mycoplasma pneumoniae elongation factor Tu interacts with fibronectin. Infect Immun76:3116–3123
    [Google Scholar]
  7. Bansal R., Deobald L. A., Crawford R. L., Paszczynski A. J.. 2009; Proteomic detection of proteins involved in perchlorate and chlorate metabolism. Biodegradation20:603–620
    [Google Scholar]
  8. Barel M., Hovanessian A. G., Meibom K., Briand J. P., Dupuis M., Charbit A.. 2008; A novel receptor–ligand pathway for entry of Francisella tularensis in monocyte-like THP-1 cells: interaction between surface nucleolin and bacterial elongation factor Tu. BMC Microbiol8:145
    [Google Scholar]
  9. Beare P. A., Chen C., Bouman T., Pablo J., Unal B., Cockrell D. C., Brown W. C., Barbian K. D., Porcella S. F.. other authors 2008; Candidate antigens for Q fever serodiagnosis revealed by immunoscreening of a Coxiella burnetii protein microarray. Clin Vaccine Immunol15:1771–1779
    [Google Scholar]
  10. Beare P. A., Unsworth N., Andoh M., Voth D. E., Omsland A., Gilk S. D., Williams K. P., Sobral B. W., Kupko J. J.. other authors 2009; Comparative genomics reveal extensive transposon-mediated genomic plasticity and diversity among potential effector proteins within the genus Coxiella . Infect Immun77:642–656
    [Google Scholar]
  11. Boonjakuakul J. K., Gerns H. L., Chen Y. T., Hicks L. D., Minnick M. F., Dixon S. E., Hall S. C., Koehler J. E.. 2007; Proteomic and immunoblot analyses of Bartonella quintana total membrane proteins identify antigens recognized by sera from infected patients. Infect Immun75:2548–2561
    [Google Scholar]
  12. Coleman S. A., Fisher E. R., Cockrell D. C., Voth D. E., Howe D., Mead D. J., Samuel J. E., Heinzen R. A.. 2007; Proteome and antigen profiling of Coxiella burnetii developmental forms. Infect Immun75:290–298
    [Google Scholar]
  13. Connolly J. P., Comerci D., Alefantis T. G., Walz A., Quan M., Chafin R., Grewal P., Mujer C. V., Ugalde R. A., Delvecchio V. G.. 2006; Proteomic analysis of Brucella abortus cell envelope and identification of immunogenic candidate proteins for vaccine development. Proteomics6:3767–3780
    [Google Scholar]
  14. Eberhardt C., Engelmann S., Kusch H., Albrecht D., Hecker M., Autenrieth I. B., Kempf V. A. J.. 2009; Proteomic analysis of the bacterial pathogen Bartonella henselae and identification of immunogenic proteins for serodiagnosis. Proteomics9:1967–1981
    [Google Scholar]
  15. Gilmore R. D. Jr, Carpio A. M., Kosoy M. Y., Gage K. L.. 2003; Molecular characterization of the sucB gene encoding the immunogenic dihydrolipoamide succinyltransferase protein of Bartonella vinsonii subsp. berkhoffi and Bartonella quintana . Infect Immun71:4818–4822
    [Google Scholar]
  16. Hackstadt T., Peacock M. G., Hitchkock P. J., Cole R. L.. 1985; Lipopolysaccharide variation in Coxiella burnetii : intrastrain heterogeneity in structure and antigenicity. Infect Immun48:359–365
    [Google Scholar]
  17. Hartley M. G., Green M., Choules G., Rogers D., Rees D. G. C., Newstead S., Sjostedt A., Titball R. W.. 2004; Protection afforded by heat shock protein 60 from Francisella tularensis is due to copurified lipopolysaccharide. Infect Immun72:4109–4113
    [Google Scholar]
  18. Hendrix L. R., Mallavia L. P.. 1984; Active transport of proline by Coxiella burnetii . J Gen Microbiol130:2857–2863
    [Google Scholar]
  19. Hendrix L. R., Mallavia L. P., Samuel J. E.. 1993; Cloning and sequencing of Coxiella burnetii outer membrane protein gene com1 . Infect Immun61:470–477
    [Google Scholar]
  20. Hoover T. A., Culp D. W., Vodkin M. H., Williams J. C., Thompson H. A.. 2002; Chromosomal DNA deletions explain phenotypic characteristics of two antigenic variants, phase II and RSA 514 (Crazy), of the Coxiella burnetii Nine Mile strain. Infect Immun70:6726–6733
    [Google Scholar]
  21. Izzo A. A., Marmion B. P., Hackstadt T.. 1991; Analysis of the cells involved in the lymphoproliferative response to Coxiella burnetii antigens. Clin Exp Immunol85:98–108
    [Google Scholar]
  22. Janovská S., Pávková I., Hubálek M., Lenčo J., Macela A., Stulík J.. 2007; Identification of immunoreactive antigens in membrane proteins enriched fraction from Francisella tularensis LVS. Immunol Lett108:151–159
    [Google Scholar]
  23. Knaust A., Weber M. V. R., Hammerschmidt S., Bergmann S., Frosch M., Kurzai O.. 2007; Cytosolic proteins contribute to surface plasminogen recruitment of Neisseria meningitidis . J Bacteriol189:3246–3255
    [Google Scholar]
  24. Li Q., Niu D., Wen B., Chen M., Qiu L., Zhang J.. 2005; Protective immunity against Q fever induced with recombinant P1 antigen fused with HspB of Coxiella burnetii . Ann N Y Acad Sci1063:130–142
    [Google Scholar]
  25. Lopez J. E., Siems W. F., Palmer G. H., Brayton K. A., McGuire T. C., Norimine J., Brown W. C.. 2005; Identification of novel antigenic proteins in a complex Anaplasma marginale outer membrane immunogen by mass spectrometry and genome mapping. Infect Immun73:8109–8118
    [Google Scholar]
  26. Maurin M., Raoult D.. 1999; Q fever. Clin Microbiol Rev12:518–553
    [Google Scholar]
  27. Mayer F.. 2003; Cytoskeletons in prokaryotes. Cell Biol Int27:429–438
    [Google Scholar]
  28. Noh S. M., Brayton K. A., Brown W. C., Norimine J., Munske G. R., Davitt C. M., Palmer G. H.. 2008; Composition of the surface proteome of Anaplasma marginale and its role in protective immunity induced by outer membrane immunization. Infect Immun76:2219–2226
    [Google Scholar]
  29. Ogawa M., Renesto P., Azza S., Moinier D., Fourquet P., Gorvel J. P., Raoult D.. 2007; Proteome analysis of Rickettsia felis highlights the expression profile of intracellular bacteria. Proteomics7:1232–1248
    [Google Scholar]
  30. Poznanovic S., Schwall G., Zengerling H., Cahill M. A.. 2005; Isoelectric focusing in serial immobilized pH gradient gels to improve protein separation in proteomic analysis. Electrophoresis26:3185–3190
    [Google Scholar]
  31. Russell-Lodrigue K. E., Zhang G. Q., McMurray D. N., Samuel J. E.. 2006; Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever. Infect Immun74:6085–6091
    [Google Scholar]
  32. Russell-Lodrigue K. E., Andoh M., Poels W. J., Shive H. R., Weeks B. R., Zhang G. Q., Tersteeg C., Masegi T., Hotta A.. other authors 2009; Coxiella burnetii isolates cause genogroup-specific virulence in mouse and guinea pig models of acute Q fever. Infect Immun77:5640–5650
    [Google Scholar]
  33. Samoilis G., Psaroulaki A., Vougas K., Tselentis Y., Tsiotis G.. 2007; Analysis of whole cell lysate from the intracellular bacterium Coxiella burnetii using two gel-based protein separation techniques. J Proteome Res6:3032–3041
    [Google Scholar]
  34. Sekeyová Z., Kowalczewska M., Decloquement P., Pelletier N., , Špitalská E., Raoult D.. 2009; Identification of protein candidates for the serodiagnosis of Q fever endocarditis by an immunoproteomic approach. Eur J Clin Microbiol Infect Dis28:287–295
    [Google Scholar]
  35. Seshadri R., Hendrix L. R., Samuel J. E.. 1999; Differential expression of translational elements by life cycle variants of Coxiella burnetii . Infect Immun67:6026–6033
    [Google Scholar]
  36. Seshadri R., Paulsen I. T., Eisen J. A., Read T. D., Nelson K. E., Nelson W. C., Ward N. L., Tettelin H., Davidsen T. M.. other authors 2003; Complete genome sequence of the Q-fever pathogen Coxiella burnetii . Proc Natl Acad Sci U S A100:5455–5460
    [Google Scholar]
  37. Shannon J. G., Heinzen R. A.. 2009; Adaptive immunity to the obligate intracellular pathogen Coxiella burnetii . Immunol Res43:138–148
    [Google Scholar]
  38. Shannon J. G., Cockrell D. C., Takahashi K., Stahl G. L., Heinzen R. A.. 2009; Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent. BMC Immunol10:26
    [Google Scholar]
  39. Tzeng Y. L., Datta A., Strole C., Kumar Kollie V. S., Birck M. R., Taylor W. P., Carlson R. W., Woodard R. W., Stephens D. S.. 2002; KpsF is the arabinose-5-phosphate isomerase required for 3-deoxy-d-manno-octulosonic acid biosynthesis and for both lipooligosaccharide assembly and capsular polysaccharide expression in Neisseria meningiditis . J Biol Chem277:24103–24113
    [Google Scholar]
  40. Vigil A., Ortega R., Nakajima-Sasaki R., Pablo J., Molina D. M., Chao C. C., Chen H. W., Ching W. M., Felgner P. L.. 2010; Genome-wide profiling of humoral immune response to Coxiella burnetii infection by protein array. Proteomics10:2259–2269
    [Google Scholar]
  41. Vodkin M. H., Williams J. C.. 1986; Overlapping deletion in two spontaneous phase variants of Coxiella burnetii . J Gen Microbiol132:2587–2594
    [Google Scholar]
  42. Voth D. E., Heinzen R. A.. 2007; Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii . Cell Microbiol9:829–840
    [Google Scholar]
  43. Waag D. M., England M. J., Pitt M. L. M.. 1997; Comparative efficacy of a Coxiella burnetii chloroform : methanol residue (CMR) vaccine and a licensed cellular vaccine (Q-Vax) in rodents challenged by aerosol. Vaccine15:1779–1783
    [Google Scholar]
  44. Waag D. M., England M. J., Tammariello R. F., Byrne W. R., Gibbs P., Banfield C. M., Pitt M. L. M.. 2002; Comparative efficacy and immunogenicity of Q fever chloroform : methanol residue (CMR) and phase I cellular (Q-Vax) vaccines in cyanomolgus monkeys challenged by aerosol. Vaccine20:2623–2634
    [Google Scholar]
  45. Williams J. C., Cantrell J. L.. 1982; Biological and immunological properties of Coxiella burnetii vaccines in C57BL/10ScN endotoxin-nonresponder mice. Infect Immun35:1091–1102
    [Google Scholar]
  46. Williams J. C., Peacock M. G., McCaul T. F.. 1981; Immunological and biological characterization of Coxiella burnetii , phases I and II, separated from host components. Infect Immun32:840–851
    [Google Scholar]
  47. Williams J. C., Damrow T. A., Wagg D. M., Amano K. I.. 1986; Characterization of phase I Coxiella burnetii chloroform-methanol residue vaccine that induces active immunity against Q fever in C57BL/10 mice. Infect Immun51:851–858
    [Google Scholar]
  48. Williams J. C., Hoover T. A., Waag D. M., Banerjee-Bhatnagar N., Bolt C. R., Scott G. H.. 1990; Antigenic structure of Coxiella burnetii . A comparison of lipopolysaccharide and protein antigens as vaccines against Q fever. Ann N Y Acad Sci590:370–380
    [Google Scholar]
  49. Xolalpa W., Vallecillo A. J., Lara M., Mendoza-Hernandez G., Comini M., Spallek R., Singh M., Espitia C.. 2007; Identification of novel bacterial plasminogen-binding proteins in the human pathogen Mycobacterium tuberculosis . Proteomics7:3332–3341
    [Google Scholar]
  50. Zhang G. Q., Samuel J. E.. 2003; Identification and cloning potentially protective antigens of Coxiella burnetii using sera from mice experimentally infected with Nine Mile phase I. Ann N Y Acad Sci990:510–520
    [Google Scholar]
  51. Zhang Y. X., Zhi N., Yu S. R., Li Q. J., Yu G. Q., Zhang X.. 1994; Protective immunity induced by 67 K outer membrane protein of phase I Coxiella burnetii in mice and guinea pigs. Acta Virol38:327–332
    [Google Scholar]
  52. Zhang G., Russell-Lodrigue K. E., Andoh M., Zhang Y., Hendrix L. R., Samuel J. E.. 2007; Mechanisms of vaccine-induced protective immunity against Coxiella burnetii infection in BALB/c mice. J Immunol179:8372–8380
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.043513-0
Loading
/content/journal/micro/10.1099/mic.0.043513-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error