Rickettsial Palindromic Elements
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''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 "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 undertook ...
, 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 of living eukaryotic host cells (typically endothelial 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 Ernest William Goodpasture (October 17, 1886 – September 20, 1960) was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of ricketts ...
and his colleagues at Vanderbilt University 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 arthropods, 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, ...
, ticks, fleas, and
lice Louse ( : lice) is the common name for any member of the clade Phthiraptera, which contains nearly 5,000 species of wingless parasitic insects. Phthiraptera has variously been recognized as an order, infraorder, or a parvorder, as a result o ...
, 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 the ...
,
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 '' Ricketts ...
,
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 * Flinde ...
, 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. Onse ...
( Australian tick typhus). The majority of pathogenic ''Rickettsia'' bacteria are susceptible to
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s of the tetracycline group.


Classification

The classification of ''Rickettsia'' into three groups (spotted fever, typhus, and scrub typhus) was initially based on serology. This grouping has since been confirmed by
DNA sequencing DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...
. All three of these groups include human pathogens. 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 arthropods,
leech Leeches are segmented parasitic or predatory worms that comprise the subclass Hirudinea within the phylum Annelida. They are closely related to the oligochaetes, which include the earthworm, and like them have soft, muscular segmented bodie ...
es, and protists. Divisions have also been identified in the spotted fever group and this group likely should be divided into two
clade A clade (), also known as a monophyletic group or natural group, is a group of organisms that are monophyletic – that is, composed of a common ancestor and all its lineal descendants – on a phylogenetic tree. Rather than the English term, ...
s. . Arthropod-inhabiting rickettsiae are generally associated with reproductive manipulation (such as parthenogenesis) 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 confusion or ...
in a woman caused by ''
Rickettsia helvetica ''Rickettsia helvetica'', previously known as the Swiss agent, is a bacterium found in ''Dermacentor reticulatus'' and other ticks, which has been implicated as a suspected but unconfirmed human pathogen. First recognized in 1979 in ''Ixodes rici ...
'' 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 inf ...
'' (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 the ...
:* ''
Rickettsia conorii ''Rickettsia conorii'' is a Gram-negative, obligate intracellular bacterium of the genus ''Rickettsia'' that causes human disease called boutonneuse fever, Mediterranean spotted fever, Israeli tick typhus, Astrakhan spotted fever, Kenya tick ty ...
'' (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 '' Ricketts ...
:* ''
Rickettsia sibirica ''Rickettsia sibirica'' is a species of ''Rickettsia''. This bacterium is the etiologic agent of North Asian tick typhus, which is also known as Siberian tick typhus. The ticks that transmit it are primarily various species of ''Dermacentor'' ...
'' (Siberia, Mongolia, northern China) :: Siberian tick typhus or North Asian tick typhus :* ''
Rickettsia australis ''Rickettsia australis'' is a bacterium that causes a medical condition called Queensland tick typhus. The probable vectors are the tick species, ''Ixodes holocyclus'' and '' Ixodes tasmani''. Small marsupials are suspected reservoirs of this b ...
'' (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. Onset ...
:* ''
Rickettsia felis ''Rickettsia felis'' is a species of bacterium, the pathogen that causes cat-flea typhus in humans, also known as flea-borne spotted fever. ''Rickettsia felis'' also is regarded as the causative organism of many cases of illnesses generally class ...
'' (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 furuncle A boil, also called a furuncle, is a deep folliculitis, which is an infection of the hair follicle. It is most commonly caus ...
:* ''
Rickettsia japonica ''Rickettsia japonica'' 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 ...
'' (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 * List ...
:* ''
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 "rickett ...
'' (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, ''Diaphorina ...
:* 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 furth ...
'' spp. :* Peach phony RLO :*
Papaya Bunchy Top Disease Papaya Bunchy Top Disease was first discovered in 1931 in Puerto Rico.Davis, M. J. 1996 Early on, the identity of the pathogen was highly contested due to the inability of isolating it; thus Koch’s postulates could not be fulfilled. Scientists h ...
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 Intracellular parasites are microparasites that are capable of growing and reproducing inside the cells of a host. Types of parasites There are two main types of intracellular parasites: Facultative and Obligate. Facultative intracellular para ...
and invade vascular endothelial cells in target organs, damaging them and producing increased vascular permeability with consequent oedema, hypotension, 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, o ...
.


Genomics

Certain segments of rickettsial genomes resemble those of
mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
. The deciphered genome of ''R. prowazekii'' is 1,111,523 bp long and contains 834
genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. Unlike free-living bacteria, it contains no genes for anaerobic
glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...
or genes involved in the biosynthesis and regulation of amino acids and nucleosides. In this regard, it is similar to mitochondrial genomes; in both cases, nuclear (host) resources are used.
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...
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 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 ''Orientia tsutsugamushi'' (from Japanese ''tsutsuga'' meaning "illness", and ''mushi'' meaning "insect") is a mite-borne bacterium belonging to the family Rickettsiaceae and is responsible for a disease called scrub typhus in humans. It is a ...
'', 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 Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...
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 Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characterist ...
. 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 Mutation Frequency Decline (''mfd'') is the gene which encodes the protein Mfd (also known as Transcription Repair Coupling Factor, TRCF). Mfd functions in transcription-coupled repair to remove a stalled RNA polymerase that has encountered DNA da ...
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 A sigma factor (σ factor or specificity factor) is a protein needed for initiation of transcription in bacteria. It is a bacterial transcription initiation factor that enables specific binding of RNA polymerase (RNAP) to gene promoters. It is ho ...
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 enzyme. It is composed of two nonidentical subunit ...
. 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 and ...
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 undertook ...
(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 Id ...
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
NIAID


from th
Centers for Disease Control and Prevention
{{Authority control Rickettsiaceae Bacteriology Bacteria genera Pathogenic bacteria