Ehrlichia

History

The genus Ehrlichia is named after a German microbiologist Paul Ehrlich.The first ehrlichial disease was first recognized in South Africa during the 19th century. Its tick-borne nature was determined in 1900. The organism itself was demonstrated 1925 when it was recognized to be a Rickettsia. It was initially named Rickettsia ruminantium, and is currently named Ehrlichia ruminantium. In 1945 a "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 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. 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.

Evolution

Ehrlichia have evolved greatly since they first emerged. The evolution in their genome has taken many different pathways, some of which have led to an increase in fitness and survival.

The Ehrlichia genome contains many different variants of genes that encode outer membrane proteins. These genes have gone through intense modification over long periods of time. Truncation is the most common modification that may result in a change in protein structure. Truncation can alter protein translation and provide antigenic variants to the organism. These truncated genes could have been the result of a fusion event of two short open reading frames or by a fission event. After the gene has been truncated and duplicated, the resulting protein's structure may be different than the original. This has a profound effect on the fitness of an organism. The survival of Ehrlichia depends greatly on the immune response of its host. With a higher range of outer-membrane proteins, the parasite 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. These repeats vary highly among individuals and species. Over time, individuals may expand or contract parts of their genes and alleles which adds genetic variation and may sometimes affect phenotype.

Ehrlichia and their closely related species Anaplasma show extreme diversity in the structure and content of their genomes. This diversity is direct result of rare clones with extreme genomes that emerged by chance after repeated bottleneck events, and this diversity persists because of the lack of selective constraints on rapid growth inside the host tissue.

Ehrlichia ruminantium

The evolutionary changes in the outer membrane proteins have led to the emergence of new strains which can infect a larger variety of hosts. Heartwater, caused by Ehrlichia ruminantium, is a prevalent tick borne disease of livestock in Africa and the Caribbean but also threatens the American mainland. Three strains have arose from this species due to evolutionary change in their genomes. When sequencing their genomes, there were many active genomic modifications such as high substitution rates, truncated genes, and the presence of pseudogenes and tandem repeats. When analyzing substitution rates between the three strains in 888 orthologous coding DNA sequences, it was observed that there were only 3 coding DNA sequences that were biased towards non-synonymous substitutions that affect phenotype. In contrast, 181 coding DNA sequences were biased towards synonymous substitutions which do not affect phenotype. This indicates there was a selection pressure to maintain protein function, and this selection acted against the non-synonymous mutations.

Ehrlichia ruminantium

The evolutionary changes in the outer membrane proteins have led to the emergence of new strains which can infect a larger variety of hosts. Heartwater, caused by Ehrlichia ruminantium, is a prevalent tick borne disease of livestock in Africa and the Caribbean but also threatens the American mainland. Three strains have arose from this species due to evolutionary change in their genomes. When sequencing their genomes, there were many active genomic modifications such as high substitution rates, truncated genes, and the presence of pseudogenes and tandem repeats. When analyzing substitution rates between the three strains in 888 orthologous coding DNA sequences, it was observed that there were only 3 coding DNA sequences that were biased towards non-synonymous substitutions that affect phenotype. In contrast, 181 coding DNA sequences were biased towards synonymous substitutions which do not affect phenotype. This indicates there was a selection pressure to maintain protein function, and this selection acted against the non-synonymous mutations.

Ehrlichia canis

Ehrlichia canis are small, obligate intracelllar, tick transmitted, gram-negative, α-proteobacterium. This species is responsible for the globally distributed canine monocytic ehrlichiosis. Ehrlichia canis also show evolution in their 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 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.

There is also the presence of reductive evolution in the Ehrlichia canis. The genome has had a severe loss of metabolic pathway enzymes compared to its ancestors. Natural selection may not be the reason for small genomes. Reductive evolution in obligate intracellar pathogens is usually the direct result of genetic drift in small populations, low recombination rates, and high mutation rates. The host metabolic pathway enzymes take control of the functions lost due to reductive evolution, and this contributes to the Ehrlichia's need for a host.

Epidemiology

Despite there being multiple strains of ehrlichiosis, there are only two strains, Ehrlichia chaffeensis and Ehrlichia ewingii, that are currently known to cause the disease in humans.

Amblyomma americanum ticks spread the E. chaffeensis and E. ewingii strains of the Ehrlichiosis bacterial infection in the Eastern and Southeastern areas of the 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 period, 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 it was discovered that neither of these cases were E. chaffeensis or E.ewingii, but instead it revealed a new species similar in genetic makeup to the E. muris strain.Ixodes Scapularis ticks are hypothesized to be the transmitting vector of the E. muris strain in these states.

See also