Coxiella burnetti
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''Coxiella burnetii'' is an obligate intracellular
bacterial Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were amon ...
pathogen, and is the causative agent of
Q fever Q fever or query fever is a disease caused by infection with ''Coxiella burnetii'', a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including ...
. The genus ''Coxiella'' is morphologically similar to ''
Rickettsia ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The term "ricke ...
'', but with a variety of genetic and physiological differences. ''C. burnetii'' is a small
Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
, 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. It can survive standard disinfectants, and is resistant to many other environmental changes like those presented in the
phagolysosome In biology, a phagolysosome, or endolysosome, is a cytoplasmic body formed by the fusion of a phagosome with a lysosome in a process that occurs during phagocytosis. Formation of phagolysosomes is essential for the intracellular destruction of mic ...
.


History and naming

Research in the 1920s and 1930s identified what appeared to be a new type of ''Rickettsia'', isolated from
tick Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...
s, that was able to pass through
filters Filter, filtering or filters may refer to: Science and technology Computing * Filter (higher-order function), in functional programming * Filter (software), a computer program to process a data stream * Filter (video), a software component tha ...
. The first description of what may have been ''Coxiella burnetii'' was published in 1925 by
Hideyo Noguchi , also known as , was a prominent Japanese bacteriologist who in 1911 discovered the agent of syphilis as the cause of progressive paralytic disease. Early life Noguchi Hideyo whose childhood name was Seisaku Noguchi was born to a family of farm ...
, 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 Sir Frank Macfarlane Burnet, (3 September 1899 – 31 August 1985), usually known as Macfarlane or Mac Burnet, was an Australian virologist known for his contributions to immunology. He won a Nobel Prize in 1960 for predicting acquired immun ...
in Australia, and Herald Rea Cox and Gordon Davis at the
Rocky Mountain Laboratory Rocky Mountain Laboratories (RML) is part of the NIH Intramural Research Program and is located in Hamilton, Montana. Operated by the National Institute of Allergy and Infectious Diseases, RML conducts research on maximum containment pathogens s ...
(RML) in the United States. 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. Research in the 1960s1970s by French Canadian-American microbiologist and
virologist Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, thei ...
Paul Fiset was instrumental in the development of the first successful Q fever vaccine. ''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.


Pathogenesis

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. 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 Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...
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. 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. 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
endosome Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
s.


Use as a biological weapon

The United States ended its
biological warfare Biological warfare, also known as germ warfare, is the use of biological toxins or infectious agents such as bacteria, viruses, insects, and fungi with the intent to kill, harm or incapacitate humans, animals or plants as an act of war. ...
program in 1969. When it did, ''C. burnetii'' was one of seven agents it had standardized as biological weapons.


Genomics

At least ten completely sequenced genomes of ''Coxiella burnetii'' strains exist, 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 An intergenic region is a stretch of DNA sequences located between genes. Intergenic regions may contain functional elements and junk DNA. ''Inter''genic regions should not be confused with ''intra''genic regions (or introns), which are non-cod ...
(IGR). CbSRs 2, 3, 4 and 9 are located antisense to identified
ORF ORF or Orf may refer to: * Norfolk International Airport, IATA airport code ORF * Observer Research Foundation, an Indian research institute * One Race Films, a film production company founded by Vin Diesel * Open reading frame, a portion of the ...
s. The CbSRs are up-regulated during intracellular growth in host cells.


Additional images

File:Coxiella_burnetii_01.JPG, ''C. burnetii'', the causative agent of
Q fever Q fever or query fever is a disease caused by infection with ''Coxiella burnetii'', a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including ...


References


External links


Coxiella burnetii
genomes and related information a
PATRIC
a Bioinformatics Resource Center funded b
NIAID
{{Taxonbar, from=Q133971 Legionellales Biological weapons Gram-negative bacteria Bacteria described in 1939