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Coxiella burnetii

Coxiella burnetii is an obligate intracellular bacterial pathogen, and is the causative agent of Q fever.[1] The genus Coxiella is morphologically similar to Rickettsia, but with a variety of genetic and physiological differences. C. burnetii is a small Gram-negative, coccobacillary bacterium that is highly resistant to environmental stresses such as high temperature, osmotic pressure, and ultraviolet light. These characteristics are attributed to a small cell variant form of the organism that is part of a biphasic developmental cycle, including a more metabolically and replicatively active large cell variant form.[2] It can survive standard disinfectants, and is resistant to many other environmental changes like those presented in the phagolysosome.[3]

Coxiella burnetii
Coxiella burnetii, the bacteria that causes Q Fever.jpg
A dry fracture of a Vero cell exposing the contents of a vacuole where Coxiella burnetii is growing
Scientific classification
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C. burnetii
Binomial name
Coxiella burnetii
(Derrick 1939)
Philip 1948

History and namingEdit

Research in the 1920s and 1930s identified what appeared to be a new type of Rickettsia, isolated from ticks, that was able to pass through filters. The first description of what may have been Coxiella burnetii was published in 1925 by Hideyo Noguchi, but since his samples did not survive, it remains unclear as to whether it was the same organism. The definitive descriptions were published in the late 1930s as part of research into the cause of Q fever, by Edward Holbrook Derrick and Macfarlane Burnet in Australia, and Herald Rea Cox and Gordon Davis at the Rocky Mountain Laboratory (RML) in the United States.[4]

The RML team proposed the name Rickettsia diaporica, derived from the Greek word for having the ability to pass through filter pores, to avoid naming it after either Cox or Davis if indeed Noguchi's description had priority. Around the same time, Derrick proposed the name Rickettsia burnetii, in recognition of Burnet's contribution in identifying the organism as a Rickettsia. As it became clear that the species differed significantly from other Rickettsia, it was first elevated to a subgenus named after Cox, Coxiella, and then in 1948 to its own genus of that name, proposed by Cornelius B. Philip, another RML researcher.[4]

Coxiella was difficult to study because it could not be reproduced outside a host. However, in 2009, scientists reported a technique allowing the bacteria to grow in an axenic culture and suggested the technique may be useful for study of other pathogens.[5]

PathogenesisEdit

 
Immunohistochemical detection of C. burnetii in resected cardiac valve of a 60-year-old man with Q fever endocarditis, Cayenne, French Guiana, monoclonal antibody against C. burnetii and hematoxylin were used for staining: Original magnification ×50

The ID50 (the dose needed to infect 50% of experimental subjects) is one via inhalation; i.e., inhalation of one organism will yield disease in 50% of the population. This is an extremely low infectious dose (only 1-10 organisms required), making C. burnetii one of the most infectious known organisms.[6][7] Disease occurs in two stages: an acute stage that presents with headaches, chills, and respiratory symptoms, and an insidious chronic stage.

While most infections clear up spontaneously, treatment with tetracycline or doxycycline appears to reduce the symptomatic duration and reduce the likelihood of chronic infection. A combination of erythromycin and rifampin is highly effective in curing the disease, and vaccination with Q-VAX vaccine (CSL) is effective for prevention of it.[citation needed]

The bacteria use a type IVB secretion system known as Icm/Dot (intracellular multiplication / defect in organelle trafficking genes) to inject over 100 effector proteins into the host. These effectors increase the bacteria's ability to survive and grow inside the host cell by modulating many host cell pathways, including blocking cell death, inhibiting immune reactions, and altering vesicle trafficking.[8][9][10] In Legionella pneumophila, which uses the same secretion system and also injects effectors, survival is enhanced because these proteins interfere with fusion of the bacteria-containing vacuole with the host's degradation endosomes.[11]

Use as a biological weaponEdit

The United States ended its biological warfare program in 1969. When it did, C. burnetii was one of seven agents it had standardized as biological weapons.[12]

GenomicsEdit

At least five completely sequenced genomes of Coxiella burnetii exist,[13] which contain about 2.1 Mbp of DNA each and encode around 2,100 open reading frames; 746 (or about 35%) of these genes have no known function.

In bacteria small regulatory RNAs are activated during stress and virulence conditions. Coxiella burnetii small RNAs (CbSRs 1, 11, 12, and 14) are encoded within intergenic region (IGR). CbSRs 2, 3, 4 and 9 are located antisense to identified ORFs. The CbSRs are up-regulated during intracellular growth in host cells.[14]

Additional imagesEdit

ReferencesEdit

  1. ^ Shaw EI, Voth DE (January 2019). "Coxiella burnetii: A Pathogenic Intracellular Acidophile". Microbiology. 165 (1): 1–3. doi:10.1099/mic.0.000707. PMC 6600347. PMID 30422108.
  2. ^ Voth DE, Heinzen RA (April 2007). "Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii". Cellular Microbiology. 9 (4): 829–40. doi:10.1111/j.1462-5822.2007.00901.x. PMID 17381428.
  3. ^ Sankaran N (2000). "Coxiella burnetii". Microbes and people : an A-Z of microorganisms in our lives. Phoenix, Arizona: The Oryx Press. p. 72. ISBN 1-57356-217-3. "In contrast to other rickettsiae, which are highly sensitive and easily killed by chemical disinfectants and changes in their surroundings, C. burnetii is highly resistant" & "Q fever". Centers for Disease Control and Prevention; National Center for Infectious Diseases; Division of Viral and Rickettsial Diseases; Viral and Rickettsial Zoonoses Branch. 2003-02-13. Retrieved 2006-05-24. "The organisms are resistant to heat, drying, and many common disinfectants."
  4. ^ a b McDade JE (1990). "Historical Aspects of Q Fever". In Marrie TJ (ed.). Q Fever, Volume I: The Disease. CRC Press. pp. 5–22. ISBN 0-8493-5984-8.
  5. ^ Omsland A, Cockrell DC, Howe D, Fischer ER, Virtaneva K, Sturdevant DE, et al. (March 2009). "Host cell-free growth of the Q fever bacterium Coxiella burnetii". Proceedings of the National Academy of Sciences of the United States of America. 106 (11): 4430–4. Bibcode:2009PNAS..106.4430O. doi:10.1073/pnas.0812074106. PMC 2657411. PMID 19246385.
  6. ^ Tigertt WD, Benenson AS, Gochenour WS (September 1961). "Airborne Q fever". Bacteriological Reviews. 25: 285–93. PMC 441106. PMID 13921201.
  7. ^ "Q fever caused by Coxiella burnetii". Centers for Disease Control.
  8. ^ Lührmann A, Nogueira CV, Carey KL, Roy CR (November 2010). "Inhibition of pathogen-induced apoptosis by a Coxiella burnetii type IV effector protein". Proceedings of the National Academy of Sciences of the United States of America. 107 (44): 18997–9001. Bibcode:2010PNAS..10718997L. doi:10.1073/pnas.1004380107. PMC 2973885. PMID 20944063.
  9. ^ Clemente TM, Mulye M, Justis AV, Nallandhighal S, Tran TM, Gilk SD (October 2018). Freitag NE (ed.). "Coxiella burnetii Blocks Intracellular Interleukin-17 Signaling in Macrophages". Infection and Immunity. 86 (10). doi:10.1128/IAI.00532-18. PMC 6204741. PMID 30061378.
  10. ^ Newton HJ, Kohler LJ, McDonough JA, Temoche-Diaz M, Crabill E, Hartland EL, Roy CR (July 2014). Valdivia RH (ed.). "A screen of Coxiella burnetii mutants reveals important roles for Dot/Icm effectors and host autophagy in vacuole biogenesis". PLoS Pathogens. 10 (7): e1004286. doi:10.1371/journal.ppat.1004286. PMC 4117601. PMID 25080348.
  11. ^ Pan X, Lührmann A, Satoh A, Laskowski-Arce MA, Roy CR (June 2008). "Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors". Science. 320 (5883): 1651–4. Bibcode:2008Sci...320.1651P. doi:10.1126/science.1158160. PMC 2514061. PMID 18566289.
  12. ^ Croddy, Eric C.; Hart, C. Perez-Armendariz J. (2002). Chemical and Biological Warfare. Springer. pp. 30–31. ISBN 0-387-95076-1.
  13. ^ "Coxiella genomes in the PATRIC database". Archived from the original on 10 September 2014. Retrieved 1 October 2012.
  14. ^ Warrier I, Hicks LD, Battisti JM, Raghavan R, Minnick MF (2014). "Identification of novel small RNAs and characterization of the 6S RNA of Coxiella burnetii". PLOS ONE. 9 (6): e100147. Bibcode:2014PLoSO...9j0147W. doi:10.1371/journal.pone.0100147. PMC 4064990. PMID 24949863.

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