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''Rickettsia'' is a
genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...
of nonmotile,
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 ...
, nonspore-forming, highly pleomorphic
bacteria 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 am ...
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 "rickettsia" has nothing to do with rickets (which is a deficiency disease resulting from lack of vitamin D); the bacterial genus ''Rickettsia'' instead was named after
Howard Taylor Ricketts Howard Taylor Ricketts (February 9, 1871 – May 3, 1910) was an American pathologist after whom the family Rickettsiaceae and the order Rickettsiales are named. He was born in Findlay, Ohio. In the early part of his career, Ricketts undertoo ...
, in honor of his pioneering work on tick-borne spotted fever. Properly, ''Rickettsia'' is the name of a single genus, but the informal term "rickettsia", plural "rickettsias", usually not capitalised, commonly applies to any members of the order Rickettsiales. Being obligate intracellular bacteria, rickettsias depend on entry, growth, and replication within the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
of living
eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
host cells (typically
endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
cells). Accordingly, ''Rickettsia'' species cannot grow in artificial nutrient culture; they must be grown either in tissue or
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
cultures; typically, chicken embryos are used, following a method developed by Ernest William Goodpasture and his colleagues at
Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million ...
in the early 1930s. Many new strains or species of ''Rickettsia'' are described each year. Some ''Rickettsia'' species are pathogens of medical and veterinary interest, but many ''Rickettsia'' are non-pathogenic to vertebrates, including humans, and infect only arthropods, often non-hematophagous, such as aphids or whiteflies. Many ''Rickettsia'' species are thus arthropod-specific symbionts, but are often confused with pathogenic ''Rickettsia'' (especially in medical literature), showing that the current view in rickettsiology has a strong anthropocentric bias. Pathogenic ''Rickettsia'' species are transmitted by numerous types of
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
s, including
chigger ''Trombicula'', known as chiggers, red bugs, scrub-itch mites, or berry bugs, are small arachnids (eight-legged arthropods) in the Trombiculidae family. In their larval stage, they attach to various animals, including humans, and feed on skin, ...
,
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 ...
s,
flea Flea, the common name for the order Siphonaptera, includes 2,500 species of small flightless insects that live as external parasites of mammals and birds. Fleas live by ingesting the blood of their hosts. Adult fleas grow to about long, ...
s, and lice, and are associated with both human and plant diseases. Most notably, ''Rickettsia'' species are the pathogens responsible for typhus,
rickettsialpox Rickettsialpox is a mite-borne infectious illness caused by bacteria of the genus ''Rickettsia'' ('' Rickettsia akari''). Physician Robert Huebner and self-trained entomologist Charles Pomerantz played major roles in identifying the cause of t ...
,
boutonneuse fever Boutonneuse fever (also called, Mediterranean spotted fever, ''fièvre boutonneuse'', Kenya tick typhus, Indian tick typhus, Marseilles fever, or Astrakhan fever) is a fever as a result of a rickettsial infection caused by the bacterium ''Rickettsi ...
,
African tick-bite fever African tick bite fever (ATBF) is a bacterial infection spread by the bite of a tick. Symptoms may include fever, headache, muscle pain, and a rash. At the site of the bite there is typically a red skin sore with a dark center. The onset of sympto ...
, Rocky Mountain spotted fever,
Flinders Island spotted fever Flinders Island spotted fever is a condition characterized by a rash in approximately 85% of cases. It is associated with '' Rickettsia honei''. See also * Japanese spotted fever * North Asian tick typhus * List of cutaneous conditions * F ...
, and
Queensland tick typhus Queensland tick typhus is a zoonotic disease caused by the bacterium '' Rickettsia australis''. It is transmitted by the ticks ''Ixodes holocyclus'' and '' Ixodes tasmani''. Signs and symptoms Queensland tick typhus is a tick-borne disease. Ons ...
( Australian tick typhus). The majority of pathogenic ''Rickettsia'' bacteria are susceptible to antibiotics of the tetracycline group.


Classification

The classification of ''Rickettsia'' into three groups (spotted fever, typhus, and scrub typhus) was initially based on
serology Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
. This grouping has since been confirmed by DNA sequencing. All three of these groups include human
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
s. The scrub typhus group has been reclassified as a related new genus, ''
Orientia ''Orientia'' is a genus of bacteria in family Rickettsiaceae. They are obligate intracellular, gram-negative bacteria found in insects and mammals. They are spread through the bites or feces of infected insects. The genus comprises the species ...
'', but they still are in the order Rickettsiales and accordingly still are grouped with the rest of the rickettsial diseases. Rickettsias are more widespread than previously believed and are known to be associated with
arthropod Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
s, leeches, and
protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the e ...
s. Divisions have also been identified in the spotted fever group and this group likely should be divided into two clades. . Arthropod-inhabiting rickettsiae are generally associated with reproductive manipulation (such as
parthenogenesis Parthenogenesis (; from the Greek grc, παρθένος, translit=parthénos, lit=virgin, label=none + grc, γένεσις, translit=génesis, lit=creation, label=none) is a natural form of asexual reproduction in which growth and developmen ...
) to persist in host lineage. In March 2010, Swedish researchers reported a case of
bacterial meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusi ...
in a woman caused by '' Rickettsia helvetica'' previously thought to be harmless.


Spotted fever group

:* '' Rickettsia rickettsii'' (Western Hemisphere) :: Rocky Mountain spotted fever :* ''
Rickettsia akari ''Rickettsia akari'' is a species of ''Rickettsia'' which causes rickettsialpox. After a 1946 outbreak of a rickettsial-type disease at an apartment complex in Kew Gardens, Queens, an investigation was performed to identify the source of the in ...
'' (USA, former Soviet Union) ::
Rickettsialpox Rickettsialpox is a mite-borne infectious illness caused by bacteria of the genus ''Rickettsia'' ('' Rickettsia akari''). Physician Robert Huebner and self-trained entomologist Charles Pomerantz played major roles in identifying the cause of t ...
:* '' Rickettsia conorii'' (Mediterranean countries, Africa, Southwest Asia, India) ::
Boutonneuse fever Boutonneuse fever (also called, Mediterranean spotted fever, ''fièvre boutonneuse'', Kenya tick typhus, Indian tick typhus, Marseilles fever, or Astrakhan fever) is a fever as a result of a rickettsial infection caused by the bacterium ''Rickettsi ...
:* '' Rickettsia sibirica'' (Siberia, Mongolia, northern China) :: Siberian tick typhus or North Asian tick typhus :* '' Rickettsia australis'' (Australia) ::
Australian tick typhus Queensland tick typhus is a zoonotic disease caused by the bacterium '' Rickettsia australis''. It is transmitted by the ticks ''Ixodes holocyclus'' and '' Ixodes tasmani''. Signs and symptoms Queensland tick typhus is a tick-borne disease. On ...
:* '' Rickettsia felis'' (North and South America, Southern Europe, Australia) ::
Flea-borne spotted fever Flea-borne spotted fever or California pseudotyphus is a condition characterized by a rash of maculopapules or furuncles. It is caused by ''Rickettsia felis''. See also * American tick bite fever * Japanese spotted fever * List of cutaneous c ...
:* ''
Rickettsia japonica ''Rickettsia japonica'' is a species of '' Rickettsia''. It can cause Japanese spotted fever Japanese spotted fever is a condition characterized by a rash that has early macules, and later, in some patients, petechiae. It is caused by '' Ricke ...
'' (Japan) ::
Oriental spotted fever Japanese spotted fever is a condition characterized by a rash that has early macules, and later, in some patients, petechiae. It is caused by '' Rickettsia japonica''. See also * Flea-borne spotted fever * Flinders Island spotted fever Flind ...
:* ''
Rickettsia africae ''Rickettsia africae'' is a species of ''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), ...
'' (South Africa) ::
African tick bite fever African tick bite fever (ATBF) is a bacterial infection spread by the bite of a tick. Symptoms may include fever, headache, muscle pain, and a rash. At the site of the bite there is typically a red skin sore with a dark center. The onset of sympto ...
:* ''
Rickettsia hoogstraalii ''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 "ricket ...
'' (Croatia, Spain and Georgia USA) :: Unknown pathogenicity


Typhus group

:* '' Rickettsia prowazekii'' (worldwide) :: Epidemic typhus, recrudescent typhus, and sporadic typhus :* '' Rickettsia typhi'' (worldwide) :: Murine typhus (endemic typhus)


Scrub typhus group

:* The causative agent of scrub typhus formerly known as ''R. tsutsugamushi'' has been reclassified into the genus ''
Orientia ''Orientia'' is a genus of bacteria in family Rickettsiaceae. They are obligate intracellular, gram-negative bacteria found in insects and mammals. They are spread through the bites or feces of infected insects. The genus comprises the species ...
''.


Flora and fauna pathogenesis

Plant diseases have been associated with these ''Rickettsia''-like organisms (RLOs): :* Beet latent rosette RLO :* Citrus greening bacterium possibly this
citrus greening disease Citrus greening disease (; or HLB) is a disease of citrus caused by a vector-transmitted pathogen. The causative agents are motile bacteria, '' Liberibacter'' spp. The disease is vectored and transmitted by the Asian citrus psyllid, '' Diaphori ...
:* Clover leaf RLO :* Grapevine infectious necrosis RLO :* Grapevine Pierce's RLO :* Grapevine yellows RLO :* Witch's broom disease on ''
Larix Larches are deciduous conifers in the genus ''Larix'', of the family Pinaceae (subfamily Laricoideae). Growing from tall, they are native to much of the cooler temperate northern hemisphere, on lowlands in the north and high on mountains fu ...
'' spp. :* Peach phony RLO :* Papaya Bunchy Top Disease Infection occurs in nonhuman mammals; for example, species of ''Rickettsia'' have been found to afflict the South American guanaco, ''Lama guanacoe''.


Pathophysiology

Rickettsial organisms are obligate intracellular parasites and invade vascular
endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
cells in target organs, damaging them and producing increased
vascular permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells ( lymp ...
with consequent oedema,
hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...
, and
hypoalbuminaemia Hypoalbuminemia (or hypoalbuminaemia) is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or ...
.


Genomics

Certain segments of rickettsial
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
s resemble those of mitochondria. The deciphered genome of ''R. prowazekii'' is 1,111,523 bp long and contains 834 genes. Unlike free-living bacteria, it contains no genes for anaerobic glycolysis or genes involved in the biosynthesis and regulation of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s and nucleosides. In this regard, it is similar to mitochondrial genomes; in both cases, nuclear (host) resources are used. ATP production in ''Rickettsia'' is the same as that in mitochondria. In fact, of all the microbes known, the ''Rickettsia'' is probably the closest relative (in a
phylogenetic In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups ...
sense) to the mitochondria. Unlike the latter, the genome of ''R. prowazekii'', however, contains a complete set of genes encoding for the tricarboxylic acid cycle and the respiratory chain complex. Still, the genomes of the ''Rickettsia'', as well as the mitochondria, are frequently said to be "small, highly derived products of several types of reductive evolution". The recent discovery of another parallel between ''Rickettsia'' and viruses may become a basis for fighting HIV infection. Human immune response to the scrub typhus pathogen, '' Orientia tsutsugamushi'', appears to provide a beneficial effect against HIV infection progress, negatively influencing the virus replication process. A probable reason for this actively studied phenomenon is a certain degree of homology between the rickettsiae and the virus, namely, common epitope(s) due to common genome fragment(s) in both pathogens. Surprisingly, the other infection reported to be likely to provide the same effect (decrease in viral load) is the virus-caused illness dengue fever. Comparative analysis of genomic sequences have also identified five conserved signature indels in important proteins, which are uniquely found in members of the genus ''Rickettsia''. These indels consist of a four-amino-acid insertion in transcription repair coupling factor Mfd, a 10-amino-acid insertion in ribosomal protein L19, a one-amino-acid insertion in FtsZ, a one-amino-acid insertion in major sigma factor 70, and a one-amino-acid deletion in
exonuclease VII The enzyme exodeoxyribonuclease VII (EC 3.1.11.6, ''Escherichia coli'' exonuclease VII, ''E. coli'' exonuclease VII, endodeoxyribonuclease VII, exodeoxyribonuclease VII) is a bacterial exonuclease Exonucleases are enzymes that work by cleaving ...
. These indels are all characteristic of the genus and serve as molecular markers for ''Rickettsia''.
Bacterial small RNA Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis an ...
s play critical roles in virulence and stress/adaptation responses. Although their specific functions have not been discovered in ''Rickettsia'', few studies showed the expression of novel sRNA in human microvascular endothelial cells (HMEC) infected with ''Rickettsia''. Genomes of intracellular or parasitic bacteria undergo massive reduction compared to their free-living relatives. Examples include Rickettsia for alpha proteobacteria, T. whipplei for Actinobacteria, Mycoplasma for Firmicutes (the low G+C content Gram-positive), and Wigglesworthia and Buchnera for gamma proteobacteria.


Naming

The genus ''Rickettsia'' is named after
Howard Taylor Ricketts Howard Taylor Ricketts (February 9, 1871 – May 3, 1910) was an American pathologist after whom the family Rickettsiaceae and the order Rickettsiales are named. He was born in Findlay, Ohio. In the early part of his career, Ricketts undertoo ...
(1871–1910), who studied Rocky Mountain spotted fever in the
Bitterroot Valley The Bitterroot Valley is located in southwestern Montana, along the Bitterroot River between the Bitterroot Range and Sapphire Mountains, in the Northwestern United States. Geography The valley extends approximately from Lost Trail Pass in Ida ...
of Montana, and eventually died of typhus after studying that disease in Mexico City. In his early part of career, he undertook research at Northwestern University on blastomycosis. He later worked on Rocky Mountain spotted fever at the University of Chicago and Bitterroot Valley of Montana. He was so devoted to his research that on several occasions,he injected himself with pathogens to study their effects. On account of the apparent similarity between Rocky Mountain fever and typhus fever, he became occupied in investigating the latter in Chicago where the disease was epidemic, and became a victim of the epidemic in 1910. His investigations and discoveries added materially to the sum of medical knowledge .


References


External links


Rickettsia
genomes and related information a
PATRIC
a Bioinformatics Resource Center funded b
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from th
Centers for Disease Control and Prevention
{{Authority control Rickettsiaceae Bacteriology Bacteria genera Pathogenic bacteria