1887

Abstract

is a Gram-negative intracellular bacterium and is the causative agent of the zoonotic disease Q fever. Several rodent and non-human primate models of virulent phase I [Nine Mile (NM)I] have been developed, and have been used to determine the efficacy of antibiotics and vaccine candidates. However, there are several advantages to using insect models to study host–microbe interactions, such as reduced animal use, lowered cost and ease of manipulation in high containment. In addition, many laboratories use the avirulent phase II clone (NMII) to study cellular interactions and identify novel virulence determinants using genetic manipulation. We report that larvae of the greater wax moth, , were susceptible to infection with both NMI and NMII. Following subcutaneous infection, we report that intracellular bacteria were present within haemocytes and that larval death occurred in a dose-dependent manner. Additionally, we have used the model to characterize the role of the type 4 secretion system in NMII and to determine antibiotic efficacy in a non-mammalian model of disease.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.077230-0
2014-06-01
2020-01-17
Loading full text...

Full text loading...

/deliver/fulltext/micro/160/6/1175.html?itemId=/content/journal/micro/10.1099/mic.0.077230-0&mimeType=html&fmt=ahah

References

  1. Anderson A., Bijlmer H., Fournier P.‐E., Graves S., Hartzell J., Kersh G. J., Limonard G., Marrie T. J., Massung R. F..& other authors ( 2013;). Diagnosis and Management of Q Fever ‐ United States, 2013: Recommendations from CDC and the Q Fever Working Group. Atlanta, GA: Centers for Disease Control and Prevention. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6203a1.htm [CrossRef][PubMed]
    [Google Scholar]
  2. 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 [CrossRef][PubMed]
    [Google Scholar]
  3. 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 crucial for disease development in Coxiella burnetii infection in mice. Infect Immun75:3245–3255 [CrossRef][PubMed]
    [Google Scholar]
  4. Aperis G., Fuchs B. B., Anderson C. A., Warner J. E., Calderwood S. B., Mylonakis E..( 2007;). Galleria mellonella as a model host to study infection by the Francisella tularensis live vaccine strain. Microbes Infect9:729–734 [CrossRef][PubMed]
    [Google Scholar]
  5. Bailey M. S., Trinick T. R., Dunbar J. A., Hatch R., Osborne J. C., Brooks T. J., Green A. D..( 2011;). Undifferentiated febrile illnesses amongst British troops in Helmand, Afghanistan. J R Army Med Corps157:150–155 [CrossRef][PubMed]
    [Google Scholar]
  6. Beare P. A., Howe D., Cockrell D. C., Omsland A., Hansen B., Heinzen R. A..( 2009;). Characterization of a Coxiella burnetii ftsZ mutant generated by Himar1 transposon mutagenesis. J Bacteriol191:1369–1381 [CrossRef][PubMed]
    [Google Scholar]
  7. Beare P. A., Sandoz K. M., Omsland A., Rockey D. D., Heinzen R. A..( 2011a;). Advances in genetic manipulation of obligate intracellular bacterial pathogens. Front Microbiol2:97 [CrossRef][PubMed]
    [Google Scholar]
  8. Beare P. A., Gilk S. D., Larson C. L., Hill J., Stead C. M., Omsland A., Cockrell D. C., Howe D., Voth D. E., Heinzen R. A..( 2011b;). Dot/Icm type IVB secretion system requirements for Coxiella burnetii growth in human macrophages. MBio2:e00175-11 [CrossRef][PubMed]
    [Google Scholar]
  9. Beare P. A., Larson C. L., Gilk S. D., Heinzen R. A..( 2012;). Two systems for targeted gene deletion in Coxiella burnetii. Appl Environ Microbiol78:4580–4589 [CrossRef][PubMed]
    [Google Scholar]
  10. Bergin D., Reeves E. P., Renwick J., Wientjes F. B., Kavanagh K..( 2005;). Superoxide production in Galleria mellonella hemocytes: identification of proteins homologous to the NADPH oxidase complex of human neutrophils. Infect Immun73:4161–4170 [CrossRef][PubMed]
    [Google Scholar]
  11. Champion O. L., Karlyshev A. V., Senior N. J., Woodward M., La Ragione R., Howard S. L., Wren B. W., Titball R. W..( 2010;). Insect infection model for Campylobacter jejuni reveals that O-methyl phosphoramidate has insecticidal activity. J Infect Dis201:776–782[PubMed]
    [Google Scholar]
  12. Derrick E. H..( 1983;). “Q” fever, a new fever entity: clinical features, diagnosis and laboratory investigation. Rev Infect Dis5:790–800 [CrossRef][PubMed]
    [Google Scholar]
  13. Desbois A. P., Coote P. J..( 2011;). Wax moth larva (Galleria mellonella): an in vivo model for assessing the efficacy of antistaphylococcal agents. J Antimicrob Chemother66:1785–1790 [CrossRef][PubMed]
    [Google Scholar]
  14. Dijkstra F., van der Hoek W., Wijers N., Schimmer B., Rietveld A., Wijkmans C. J., Vellema P., Schneeberger P. M..( 2012;). The 2007–2010 Q fever epidemic in The Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming. FEMS Immunol Med Microbiol64:3–12 [CrossRef][PubMed]
    [Google Scholar]
  15. Faix D. J., Harrison D. J., Riddle M. S., Vaughn A. F., Yingst S. L., Earhart K., Thibault G..( 2008;). Outbreak of Q fever among US military in western Iraq, June–July 2005. Clin Infect Dis46:e65–e68 [CrossRef][PubMed]
    [Google Scholar]
  16. Gan Y. H., Chua K. L., Chua H. H., Liu B., Hii C. S., Chong H. L., Tan P..( 2002;). Characterization of Burkholderia pseudomallei infection and identification of novel virulence factors using a Caenorhabditis elegans host system. Mol Microbiol44:1185–1197 [CrossRef][PubMed]
    [Google Scholar]
  17. Glavis-Bloom J., Muhammed M., Mylonakis E..( 2012;). Of model hosts and man: using Caenorhabditis elegans, Drosophila melanogaster and Galleria mellonella as model hosts for infectious disease research. Adv Exp Med Biol710:11–17 [CrossRef][PubMed]
    [Google Scholar]
  18. Hackstadt T., Peacock M. G., Hitchcock P. J., Cole R. L..( 1985;). Lipopolysaccharide variation in Coxiella burnetti: intrastrain heterogeneity in structure and antigenicity. Infect Immun48:359–365[PubMed]
    [Google Scholar]
  19. Harding C. R., Schroeder G. N., Reynolds S., Kosta A., Collins J. W., Mousnier A., Frankel G..( 2012;). Legionella pneumophila pathogenesis in the Galleria mellonella infection model. Infect Immun80:2780–2790 [CrossRef][PubMed]
    [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 [CrossRef][PubMed]
    [Google Scholar]
  21. Huebner R. J., Hottle G. A., Robinson E. B..( 1948;). Action of streptomycin in experimental infection with Q fever. Public Health Rep63:357–362 [CrossRef][PubMed]
    [Google Scholar]
  22. Islam A., Lockhart M., Stenos J., Graves S..( 2013;). 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 Hyg89:800–803 [CrossRef][PubMed]
    [Google Scholar]
  23. Joshua G. W., Karlyshev A. V., Smith M. P., Isherwood K. E., Titball R. W., Wren B. W..( 2003;). A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a biotic surface. Microbiology149:3221–3229 [CrossRef][PubMed]
    [Google Scholar]
  24. Komura T., Yasui C., Miyamoto H., Nishikawa Y..( 2010;). Caenorhabditis elegans as an alternative model host for Legionella pneumophila, and protective effects of Bifidobacterium infantis. Appl Environ Microbiol76:4105–4108 [CrossRef][PubMed]
    [Google Scholar]
  25. Laws T. R., Smith S. A., Smith M. P., Harding S. V., Atkins T. P., Titball R. W..( 2005;). The nematode Panagrellus redivivus is susceptible to killing by human pathogens at 37 °C. FEMS Microbiol Lett250:77–83 [CrossRef][PubMed]
    [Google Scholar]
  26. Madariaga M. G., Rezai K., Trenholme G. M., Weinstein R. A..( 2003;). Q fever: a biological weapon in your backyard. Lancet Infect Dis3:709–721 [CrossRef][PubMed]
    [Google Scholar]
  27. Marmion B..( 2007;). Q fever: the long journey to control by vaccination. Med J Aust186:164–166[PubMed]
    [Google Scholar]
  28. 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 Pathog10:e1004013 [CrossRef][PubMed]
    [Google Scholar]
  29. Maurin M., Raoult D..( 1999;). Q fever. Clin Microbiol Rev12:518–553[PubMed]
    [Google Scholar]
  30. McQuiston J. H., Childs J. E..( 2002;). Q fever in humans and animals in the United States. Vector Borne Zoonotic Dis2:179–191 [CrossRef][PubMed]
    [Google Scholar]
  31. Moodie C. E., Thompson H. A., Meltzer M. I., Swerdlow D. L..( 2008;). Prophylaxis after exposure to Coxiella burnetii. Emerg Infect Dis14:1558–1566 [CrossRef][PubMed]
    [Google Scholar]
  32. Moos A., Hackstadt T..( 1987;). Comparative virulence of intra- and interstrain lipopolysaccharide variants of Coxiella burnetii in the guinea pig model. Infect Immun55:1144–1150[PubMed]
    [Google Scholar]
  33. Newton H. J., McDonough J. A., Roy C. R..( 2013;). Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole. PLoS ONE8:e54566 [CrossRef][PubMed]
    [Google Scholar]
  34. Ochoa-Repáraz J., Sentissi J., Trunkle T., Riccardi C., Pascual D. W..( 2007;). 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 Immun75:5845–5858 [CrossRef][PubMed]
    [Google Scholar]
  35. Omsland A., Cockrell D. C., Howe D., Fischer E. R., Virtaneva K., Sturdevant D. E., Porcella S. F., Heinzen R. A..( 2009;). Host cell-free growth of the Q fever bacterium Coxiella burnetii. Proc Natl Acad Sci U S A106:4430–4434 [CrossRef][PubMed]
    [Google Scholar]
  36. Omsland A., Beare P. A., Hill J., Cockrell D. C., Howe D., Hansen B., Samuel J. E., Heinzen R. A..( 2011;). Isolation from animal tissue and genetic transformation of Coxiella burnetii are facilitated by an improved axenic growth medium. Appl Environ Microbiol77:3720–3725 [CrossRef][PubMed]
    [Google Scholar]
  37. 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 [CrossRef][PubMed]
    [Google Scholar]
  38. Schell M. A., Lipscomb L., DeShazer D..( 2008;). Comparative genomics and an insect model rapidly identify novel virulence genes of Burkholderia mallei. J Bacteriol190:2306–2313 [CrossRef][PubMed]
    [Google Scholar]
  39. Scott G. H., Williams J. C., Stephenson E. H..( 1987;). Animal models in Q fever: pathological responses of inbred mice to phase I Coxiella burnetii. J Gen Microbiol133:691–700[PubMed]
    [Google Scholar]
  40. Seitz V., Clermont A., Wedde M., Hummel M., Vilcinskas A., Schlatterer K., Podsiadlowski L..( 2003;). Identification of immunorelevant genes from greater wax moth (Galleria mellonella) by a subtractive hybridization approach. Dev Comp Immunol27:207–215 [CrossRef][PubMed]
    [Google Scholar]
  41. Shannon J. G., Howe D., Heinzen R. A..( 2005;). Virulent Coxiella burnetii does not activate human dendritic cells: role of lipopolysaccharide as a shielding molecule. Proc Natl Acad Sci U S A102:8722–8727 [CrossRef][PubMed]
    [Google Scholar]
  42. Thomas R. J., Hamblin K. A., Armstrong S. J., Müller C. M., Bokori-Brown M., Goldman S., Atkins H. S., Titball R. W..( 2013;). Galleria mellonella as a model system to test the pharmacokinetics and efficacy of antibiotics against Burkholderia pseudomallei. Int J Antimicrob Agents41:330–336 [CrossRef][PubMed]
    [Google Scholar]
  43. Vishwanath S., Hackstadt T..( 1988;). Lipopolysaccharide phase variation determines the complement-mediated serum susceptibility of Coxiella burnetii. Infect Immun56:40–44[PubMed]
    [Google Scholar]
  44. Vogel H., Altincicek B., Glöckner G., Vilcinskas A..( 2011;). A comprehensive transcriptome and immune-gene repertoire of the lepidopteran model host Galleria mellonella.. BMC Genomics12:308 [CrossRef][PubMed]
    [Google Scholar]
  45. Voth D. E., Heinzen R. A..( 2007;). Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii. Cell Microbiol9:829–840 [CrossRef][PubMed]
    [Google Scholar]
  46. Waag D. M., Byrne W. R., Estep J., Gibbs P., Pitt M. L. M., Banfield C. M..( 1999;). 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 Sci49:634–638[PubMed]
    [Google Scholar]
  47. Wand M. E., Müller C. M., Titball R. W., Michell S. L..( 2011;). Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis. BMC Microbiol11:11 [CrossRef][PubMed]
    [Google Scholar]
  48. Weber M. M., Chen C., Rowin K., Mertens K., Galvan G., Zhi H., Dealing C. M., Roman V. A., Banga S..& other authors ( 2013;). Identification of Coxiella burnetii type IV secretion substrates required for intracellular replication and Coxiella-containing vacuole formation. J Bacteriol195:3914–3924 [CrossRef][PubMed]
    [Google Scholar]
  49. Whelan J., Schimmer B., Schneeberger P., Meekelenkamp J., Ijff A., van der Hoek W., Robert-Du Ry van Beest Holle M..( 2011;). Q fever among culling workers, the Netherlands, 2009–2010. Emerg Infect Dis17:1719–1723 [CrossRef][PubMed]
    [Google Scholar]
  50. 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[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.077230-0
Loading
/content/journal/micro/10.1099/mic.0.077230-0
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