Anaplasma marginale

A Microbial Biorealm page on the genus Anaplasma marginale

Anaplasma marginale in bovine erythrocytes - "A Rickettsial agent transmitted by ticks." Photo credit: Veterinary Clinical Parasitology Images

Classification

Higher order taxa

Bacteria; Proteobacteria; Alphaproteobacteria; Rickettsiales; Anaplasmataceae

Species

NCBI: Taxonomy

Anaplasma marginale

Strains:

Anaplasma marginale str. Florida; Anaplasma marginale str. Illinois; Anaplasma marginale str. St. Maries; Anaplasma marginale str. Virginia

Other names:

Anaplasma theileri; Anaplasma rossicum; Anaplasma argentium; Anaplasma theileri Neitz 1957; Anaplasma rossicum Yakimoff and Belawine 1927; Anaplasma argentium Lignieres 1914; Anaplasma marginale Theiler 1910

Description and significance

The rickettsia Anaplasma marginale is the most prevalent tick-borne livestock pathogen worldwide and is a severe constraint to animal health. The disease results in significant morbidity and mortality in U.S. cattle and affects its exportation. Despite its global impact on animal health, there is currently no widely accepted vaccine and the live, blood-based vaccines widely used in tropical countries cannot be licensed in the U.S. due to the risk of transmitting both known and unknown pathogens. A vaccine for anaplasmosis is a priority for the USDA National Cattlemen’s Beef Association and many other research groups worldwide.

A. marginale is the type species for the genus Anaplasma which contains both animal and human pathogens. It is a rickettsia and and a tick-transmitted obligate intracellular bacteria. It can be cultured from the red blood cells of cattle. While erythrocytes seem to be the only site of infection, the bacteria undergoes a complex developmental cycle in ticks, which are then transmitted during feeding on a host cattle. The genomic information would have a broad applicability to closely related species and organisms within the same order as members of rickettsia are responsible for both animal and human diseases and deaths.

Genome structure

Circular genome of Anaplasma marginale St. Maries. Photo credit: Washington State University

Genome: Genome

Members of the order, Rickettsiales, are small, obligate intracellular bacteria that typically have small genomes, attributed to "reductive evolution" stemming from living as intracellular parasitism. Many obligate intracellular bacteria are difficult to culture, and the need to be grown in a host cell makes it difficult to obtain large amounts of organism-specific DNA necessary for whole genome sequencing. The first complete genome sequencing was done on A. Marginale St. Maries strain.

• Genes: 1005
• Protein coding: 949
• Length: 1,197,687 nt
• Structural RNAs: 40
• GC Content: 49%
• Pseudo genes: 16
• % Coding: 85%
• Topology: circular

Cell structure and metabolism

Anaplasma Marginale is a pathogenic gram-negative stain bacteria with an outer membrane composed of lipopolysaccharides. (info about gram-negative bacteria) Its class, Alphaproteobacteria (particularly the order Rickettsiales), are thought to be the precursors of the mitochondria of eukaryotic cells. According to the endosymbiotic theory, the mitochondria organelle now existant in eukaryotic cells originated as separate prokaryotic organisms which were taken inside the cell as endosymbionts. For energy, Anaplasma marginale has been shown to use pyruvate, a glycolytic product, for its metabolism.

Ecology

Specific species of cattle ticks are carriers of Anaplasma marginale The organism multiplies in the tick and will pass to later stages of the tick life cycle. However, it does not appear the infection is passed on to the eggs. Consequently, the next generation of ticks will not be infected unless they also feed on a carrier animal. As carriers, they are unaffected by the bacteria. These ticks carry this infection and infect cattle as a parasite feeding off the bood of the host. Because the adult male tick is more mobile and lives longer than other stages, it is the most likely stage to transmit the disease. Biting flies can transmit the disease but are less efficient vectors than ticks. The organism can also cross the placenta to the fetus.

Calves from immune mothers receive temporary protection (maternal antibody) from the colostrum (first milk) which prevents anaplasmosis. This protection lasts about 3 months and, in most cases, is followed by an age resistance that lasts until the animals are about 9 to 12 months old. Calves exposed to anaplasmosis when the maternal or age resistance is high, rarely show clinical symptoms but develop a solid, long lasting immunity. It is therefore possible to have both Anaplasma marginale and cattle ticks present on a property without animal losses or clinical disease. If cattle are not exposed to Anaplasma as calves, the age resistance gradually wanes and these animals will become increasingly susceptible to the disease. If susceptible adult cattle are mixed with infected cattle in the presence of the cattle tick, serious losses due to anaplasmosis can occur.

Pathology

Anaplasmosis is a form of tick fever carried by a specfic species of cattle tick. A. marginale is an obligate intracellular bacteria. As the disease progresses, infected and even uninfected red blood cells are destroyed mainly in the liver and spleen, resulting in an increasing anaemia and even death in severe cases. Any stage of the cattle tick’s life cycle can become infected after feeding on an animal carrying Anaplasma organisms in its blood stream. Therefore an infected stage of the tick must transfer to a susceptible animal for transmission to occur. The bacteria begins its course by invading and multiplying in red blood cells of the host cattle.

Clinical symptoms of infection include transient fever, weakness and respiratory distress particularly after exercise, depression and loss of appetite, jaundice, and brown urine due to bile pigments. Cattle that recover from anaplasmosis remain carriers of the organism and are immune to further disease.

Application to Biotechnology

A. Marginale is the most prevalent tick-borne pathogen of cattle with a world-wide distribution. Studies conducted in this organism are in hopes of finding vaccines against A. marginale and the relatives in the order Rickettsiales that pathogenic for both animals and humans.

Current Research

"Identification of midgut and salivary glands as specific and distinct barriers to efficient tick-borne transmission of Anaplasma marginale."

Ueti MW, Reagan JO Jr, Knowles DP Jr, Scoles GA, Shkap V, Palmer GH. April 9, 2007

There are at least two specific barriers, the midgut and salivary glands, to efficient tick-borne transmission. This inability to colonize the midgut epithelium prevented subsequent development within the salivary glands and thus prevents transmission of the A. Marginale to the host. This research highlights the complexity of the pathogen-tick interaction.

"Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins"

Brayton KA, Kappmeyer LS, Herndon DR, Dark MJ, Tibbals DL, Palmer GH, McGuire TC, Knowles DP Jr. January 18, 2005

This published the first time A. Marginale was completely sequenced. Within the mammalian host, A. marginale generates antigenic variants by changing a surface coat composed of numerous proteins. By sequencing and annotating the complete 1,197,687-bp genome of the St. Maries strain of A. marginale, it described the membrane of the organism. It found that the surface coat is dominated by two families containing immunodominant proteins: the msp2 superfamily and the msp1 superfamily.

"Outer Membrane Protein Complex of Anaplasma Marginale, Use in Vaccine Development Through Genomics"

Scoles, G., Palmer, G. USDA, Current ARS Project Start Date: Jul 31, 2003 End Date: May 31, 2008

Because of its damaging, pathogenic nature, much of the current research on this organism are on finding effective vaccines against anaplasma marginale and its relatives. The USDA (United States Department of Agriculture) Agriculture Research Service is currently studying the outer membrane protein complex to use the genomics of the organism to produce a vaccine. By targetting the outer membrane complex that contains protection-inducing proteins the vaccine would be more effective at targetting the cattle disease. The research will test whether novel outer membrane proteins induce protection against the challenge when delivered in a recombinant-based vaccine.

References

Schaechter, M., Ingraham, J. L, Neidhardt, F. C., Microbe, Washington DC., ASM Press 2006

Brayton KA, Kappmeyer LS, Herndon DR, Dark MJ, Tibbals DL, Palmer GH, McGuire TC, Knowles DP Jr., "Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins." Proc Natl Acad Sci U S A. 2005. Vol 102. p 844-9

[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17420231&query_hl=7&itool=pubmed_DocSum Ueti MW, Reagan JO Jr, Knowles DP Jr, Scoles GA, Shkap V, Palmer GH., "Identification of midgut and salivary glands as specific and distinct barriers to efficient tick-borne transmission of Anaplasma marginale." Infect Immun. 2007 April 9.

McHolland, L. E., Caldwell, D. R., "Pyruvate metabolism by Anaplasma marginale in cell-free culture". Canadian Journal of Microbiology. 1999. Vol 45. p 185-189

Washington State University - The Anaplasma marginale Genome Sequencing Project Retrieved 29 April 2007

NCBI Taxonomy Browser, "Anaplasma marginale" Retrieved 30 April, 2007

TGR-CMR, "Anaplasma marginale St. Maries Genome" Retreived 1 May, 2007

HealthGene - Molecular Diagnostic and Research Center. "D425 Anaplasma Marginale"

National Institute of Health, "Anaplasma Marginale" Retrieved 30 April, 2007

Wikipedia: "Endosymbiotic Theory" Retrieved 2 May, 2007

USDA, Current ARS Project: Outer Membrane Protein Complex of Anaplasma Marginale, Use in Vaccine Development Through Genomics Start Date: Jul 31, 2003 End Date: May 31, 2008

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Edited by Patricia Shih; student of Rachel Larsen and Kit Pogliano