''Ehrlichia'' is a

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...

Rickettsiales The Rickettsiales, informally called rickettsias, are an order of small Alphaproteobacteria. They are obligate intracellular parasites, and some are notable pathogens, including ''Rickettsia'', which causes a variety of diseases in humans, and ' ...

bacteria that are transmitted to vertebrates by ticks. These bacteria cause the disease

ehrlichiosis Ehrlichiosis is a tick-borne bacterial infection, caused by bacteria of the family Anaplasmataceae, genera '' Ehrlichia'' and ''Anaplasma''. These obligate intracellular bacteria infect and kill white blood cells. The average reported annual in ...

, which is considered

zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...

, because the main reservoirs for the disease are animals. ''Ehrlichia'' species are obligately

intracellular pathogen 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 pa ...

s and are transported between cells through the host cell

filopodia Filopodia (singular filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as ''microspikes'', and when they extend beyond the lame ...

during initial stages of infection, whereas in the final stages of infection, the pathogen ruptures the host cell membrane.

History

The genus ''Ehrlichia'' is named after German microbiologist

Paul Ehrlich Paul Ehrlich (; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology, and antimicrobial chemotherapy. Among his foremost achievements were finding a cure ...

. The first ehrlichial disease was recognized in

South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring countri ...

during the 19th century. Its tick-borne nature was determined in 1900. The organism itself was demonstrated in 1925 when it was recognized to be a ''

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 "rickett ...

''. It was initially named ''Rickettsia ruminantium'', and is currently named ''

Ehrlichia ruminantium Heartwater (also known as cowdriosis, nintas, and ehrlichiosis) is a tick-borne rickettsial disease. The name is derived from the fact that fluid can collect around the heart or in the lungs of infected animals. It is caused by ''Ehrlichia rumin ...

''. In 1945, an "infection and treatment" method for livestock was developed. This is still the only commercially available "vaccine" against the disease, which is not a true vaccine, but intentional exposure to the disease with monitoring and

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 ...

treatment if needed. In 1985, the organism was first propagated reliably in tissue culture. A new species of ''Ehrlichia'' was discovered inside the deer tick ''

Ixodes scapularis ''Ixodes scapularis'' is commonly known as the deer tick or black-legged tick (although some people reserve the latter term for ''Ixodes pacificus'', which is found on the west coast of the US), and in some parts of the US as the bear tick. It wa ...

''. This newly found organism has only been isolated from deer ticks in Wisconsin and Minnesota in the USA. The species is known as ''Ehrlichia'' Wisconsin HM543746.

Species

Accepted Species

The following species have been effectively and validly published: * ''

Ehrlichia canis ''Ehrlichia canis'' is an obligate intracellular bacterium that acts as the causative agent of ehrlichiosis, a disease most commonly affecting canine species. This pathogen is present throughout the United States (but is most prominent in the So ...

'' (Donatien and Lestoquard 1935) Moshkovski 1945 (Approved Lists 1980) * ''

Ehrlichia chaffeensis ''Ehrlichia chaffeensis'' is an obligate intracellular, Gram-negative species of Rickettsiales bacteria. It is a zoonotic pathogen transmitted to humans by the lone star tick (''Amblyomma americanum''). It is the causative agent of human monoc ...

'' Anderson ''et al''. 1992 * ''

Ehrlichia ewingii ''Ehrlichia ewingii'' is a species of rickettsiales bacteria. It has recently been associated with human infection, and can be detected via PCR serological testing. The name ''Ehrlichia ewingii'' was proposed in 1992. T ...

'' Anderson ''et al''. 1992 * '' Ehrlichia minasensis'' Cabezas-Cruz ''et al''. 2016 * ''

Ehrlichia muris ''Ehrlichia muris'' is a species of pathogenic bacteria first isolated from mice, with type strain AS145T. Its genome has been sequenced. References Further reading * * External linksLPSN*WISC entryEhrlichia risticii'' Holland ''et al''. 1985 * ''

'' (Cowdry 1925) Dumler ''et al''. 2001 * '' Ehrlichia sennetsu'' (Misao and Kobayashi 1956) Ristic and Huxsoll 1984

Provisional Species

The following species have been published, but are not valid according to the

Bacteriological Code The International Code of Nomenclature of Prokaryotes (ICNP) formerly the International Code of Nomenclature of Bacteria (ICNB) or Bacteriological Code (BC) governs the scientific names for Bacteria and Archaea.P. H. A. Sneath, 2003. A short histor ...

: * "''Ehrlichia japonica''" Lin ''et al''. 2021 * "''Ehrlichia ovina''" Moshkovski 1945 * "''Ehrlichia platys''" French and Harvey 1983

''Candidatus'' Species

The following species have been published as ''

candidatus In prokaryote nomenclature, ''Candidatus'' (Latin for candidate of Roman office) is used to name prokaryotic phyla that are well characterized but yet-uncultured. Contemporary sequencing approaches, such as 16S sequencing or metagenomics, provide m ...

'' species: * "''Candidatus'' Ehrlichia corsicanum" Cicculli ''et al''. 2020 * "''Candidatus'' Ehrlichia khabarensis" Rar ''et al''. 2015 * "''Candidatus'' Ehrlichia occidentalis" Gofton ''et al''. 2017 * "''Candidatus'' Ehrlichia ornithorhynchi" Gofton ''et al''. 2018 * "''Candidatus'' Ehrlichia ovata" Lynn ''et al''. 2019 * "''Candidatus'' Ehrlichia rustica" Ehounoud ''et al''. 2016 * "''Candidatus'' Ehrlichia senegalensis" Dahmana ''et al''. 2020 * "''Candidatus'' Ehrlichia shimanensis" Kawahara ''et al''. 2006 * "''Candidatus'' Ehrlichia urmitei" Ehounoud ''et al''. 2016 * "''Candidatus'' Ehrlichia walkeri" corrig. Brouqui ''et al''. 2003

Evolution

The ''Ehrlichia'' genome contains many different variants of genes that encode outer

membrane proteins Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

, which have gone through intense modification over long periods of time. The great diversity in outer membrane protein genes is thought to originate from gene duplication events, followed by the fusion and fission of resulting

paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

of the gene. These duplication, fusion, and fission events form multiple gene copies and fragments, which are able to accumulate mutations. These copies and fragments of membrane proteins can then recombine, through a process called

gene conversion Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces a ...

, resulting in a new gene variant. This has a profound effect on the fitness of an organism. The survival of ''Ehrlichia'' depends greatly on the

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

of its host. With a higher range of outer membrane proteins, the

parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...

can evade the immune system of the host more effectively and establish persistent infection. The most pronounced evidence of evolution in the genome size of ''Erhlichia'' is the presence of

tandem repeats Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadil ...

, which vary highly among individuals and species. Over time, individuals may expand or contract parts of their genes and

alleles An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

, which adds

genetic variation Genetic variation is the difference in DNA among individuals or the differences between populations. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources of genetic variation, ...

and may sometimes affect

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

. ''Ehrlichia'' and its closely related genus ''Anaplasma'' show extreme diversity in the structure and content of their genomes. This diversity is direct result of rare

clones Clone or Clones or Cloning or Cloned or The Clone may refer to: Places * Clones, County Fermanagh * Clones, County Monaghan, a town in Ireland Biology * Clone (B-cell), a lymphocyte clone, the massive presence of which may indicate a pathologi ...

with extreme genomes that emerged by chance after repeated

bottleneck Bottleneck literally refers to the narrowed portion (neck) of a bottle near its opening, which limit the rate of outflow, and may describe any object of a similar shape. The literal neck of a bottle was originally used to play what is now known as ...

events, and this diversity persists because of the lack of selective constraints on rapid growth inside the host tissue.

''E. ruminantium''

The evolutionary changes in the outer

have led to the emergence of new strains that can infect a larger variety of hosts. Heartwater, caused by ''E. ruminantium'', is a prevalent tick-borne disease of

livestock Livestock are the domesticated animals raised in an agricultural setting to provide labor and produce diversified products for consumption such as meat, eggs, milk, fur, leather, and wool. The term is sometimes used to refer solely to animals ...

in Africa and the Caribbean, but also threatens the American mainland. Three strains have arisen from this species due to evolutionary change in their genomes. When

sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...

their genomes,e many active genomic modifications have occurred, such as high substitution rates, truncated genes, and the presence of

pseudogenes Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are ...

and tandem repeats. When analyzing substitution rates between the three strains in 888

orthologous Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...

coding DNA sequences, three coding DNA sequences were biased towards nonsynonymous substitutions that affect phenotype. In contrast, 181 coding DNA sequences were biased towards synonymous substitutions, which do not affect phenotype. This indicates that

selection pressure Any cause that reduces or increases reproductive success in a portion of a population potentially exerts evolutionary pressure, selective pressure or selection pressure, driving natural selection. It is a quantitative description of the amount of ...

to maintain protein function existed, and this selection acted against the nonsynonymous mutations.

''E. canis''

''E. canis'' is a small, obligate-intracellular, tick-transmitted,

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 wall ...

α-proteobacterium. This species is responsible for the globally distributed canine monocytic ehrlichiosis. ''E. canis'' also shows evolution in its complex membrane structures and immune evasion strategies. These evolutionary features are derived traits that do not show up in the previous lineages, which may indicate that these features may have contributed to a fitness advantage that kept this lineage going. Unique

glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

and major outer membrane proteins can be expressed variously using 25 different genes. The glycoproteins are important targets of the host immune response, attachment to the host cell, and other features in the immune response. The more outer-membrane protein genes that can be expressed, the higher the chance the organism can avoid being recognized by the host's immune system. Also, reductive evolution is present in ''E. canis''. The genome has had a severe loss of metabolic pathway enzymes compared to its ancestors. Reductive evolution in obligate intracellular pathogens is usually the direct result of

genetic drift Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance. Genetic drift may cause gene variants to disappear completely and there ...

in small populations, low recombination rates, and high

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

rates. The host metabolic pathway enzymes take control of the functions lost due to reductive evolution, and this contributes to its need for a host. Natural selection may not be the reason for small genomes.

Epidemiology

Despite there being multiple strains of ehrlichiosis, only two species, ''E. chaffeensis'' and ''E. ewingii'', are currently known to cause the disease in humans. ''Amblyomma americanum'' ticks spread ''E. chaffeensis'' and ''E. ewingii'' bacterial infection in the Eastern and Southeastern United States, while ''A. phagocytophilum'' is spread by the ''Ixodes scapularis'' tick in the Upper Midwest; 1,518 cases of ''E. chaffeensis'' were recorded in southeastern, south-central and mid-Atlantic areas of the country in 2013. Despite the first cases of "E. ewingii" appearing in the Missouri in the year 1999, this strain was not reportable to health officials until 2008. Since 2008, there have been reported human cases of ''E. ewingii'' in Oklahoma, Arkansas and Tennessee though it is observed less frequently than ''E. chaffeensis.'' During 2008-2012, 4,613 cases of ''E. chaffeensis'' infections were reported through the National Notifiable Diseases Surveillance System (NNDSS). The incidence rate (IR) was 3.2 cases per million person-years (PYs). The hospitalization rate (HR) was 57% and the case fatality rate (CFR) was 1%. During that same time, 55 cases of ''E. ewingii'' infections were reported through NNDSS. The national IR was 0.04 cases per million PY. The HR was 77% and the case fatality rate was 0%. In Minnesota and Wisconsin, four people reported symptoms that are associated with ehrlichiosis, and upon further research, neither of these cases was found to be ''E. chaffeensis'' or ''E. ewingii'', but instead it was revealed as a new species, similar in genetic makeup to ''E. muris''. ''Ixodes scapularis'' ticks are hypothesized to be the transmitting vector of the ''E. muris'' strain in these states.

References

External links

Ehrlichia
genomes and related information a
PATRIC
a Bioinformatics Resource Center funded b
NIAID
*
Forum discution and clinical presentation (RO)
Clinical experiences about ehrlichia and coinfections at dogs in Romania

Newly discovered species of Ehrlichia found in deer ticks {{Taxonbar, from=Q138670 Rickettsiales Bacteria genera