Anaplasma marginale: Difference between revisions

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{{Biorealm Genus}}
{{Biorealm Genus}}
[[Image:anaplasmamarginale.jpg |thumb|250px|right| Anaplasma marginale in bovine erythrocytes - "A Rickettsial agent transmitted by ticks." Photo credit: [http://www.cvm.okstate.edu/~users/jcfox/htdocs/clinpara/lst21_30.htm Veterinary Clinical Parasitology Images]]]
[[Image:anaplasmamarginale.jpg |thumb|250px|right| Anaplasma marginale in bovine erythrocytes - "A Rickettsial agent transmitted by ticks." Photo credit: [http://www.cvm.okstate.edu/~users/jcfox/htdocs/clinpara/lst21_30.htm Veterinary Clinical Parasitology Images]]]
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'''Other names:'''
'''Other names:'''


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


==Description and significance==
==Description and significance==


Anaplasma marginale is the most prevalent tick-borne, livestock pathogen worldwide and is a constraint to animal health. The disease results in significant morbidity and mortality in U.S. cattle and, economically, its exportation.  Despite a global impact on animal health, there is still no widely accepted vaccine. Live vaccinations are blood-based and are widely used in tropical countries, but they cannot be licensed in the U.S. because of the risk of transmitting known and unknown pathogens. [1] An effective vaccine for anaplasmosis is a priority for the USDA National Cattlemen’s Beef Association and many other research groups.  
''Anaplasma marginale'' is the most prevalent tick-borne, livestock pathogen worldwide and poses a considerable constraint to animal health. The disease results in significant morbidity and mortality of United State's (US) cattle population, which affects the exportation of beef.  Despite a global impact on animal health, there is no widely accepted vaccine for "Anaplasma marginale." Live vaccinations are blood-based and are often used in tropical countries, but they cannot be licensed in the U.S. because of the risk of transmitting any known or unknown pathogens [1]. Thus, finding an effective vaccine for anaplasmosis is a priority for the USDA National Cattlemen’s Beef Association and many other research groups.  


A. marginale is the type species for the genus Anaplasma which contains both animal and human pathogens. It is a Rickettsiales obligate intracellular bacterium. These organisms can be easily cultured from the red blood cells of cattle. While erythrocytes seem to be the only site of infection, the bacteria undergo a complex developmental cycle in ticks, which are then transmitted during feeding on host cattle. The genomic information would have a broad applicability to closely related species and organisms within the same order, since members of Rickettsiales are responsible for both animal and human diseases and deaths.
'The genus ''Anaplasma'' which contains both animal and human pathogens. Being a Rickettsiales obligate intracellular bacterium, it requires a host in order survive. These organisms can be easily cultured from the red blood cells of cattle. While mammalian erythrocytes seem to be the only site of infection, the bacterium also undergoes a complex developmental cycle in ticks. When a tick feeds on a host cattle, the bacteria enter through the site of the bite, infecting the animal. The genomic information of the species would have a broad applicability to closely related organisms within the same order, since members of Rickettsiales are responsible for both animal and human diseases and deaths.


==Genome structure==
==Genome structure==
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Members of the order, Rickettsiales, are small, obligate intracellular bacteria that typically have small genomes due to "reductive evolution" from intracellular parasitism. Because many obligate bacteria are difficult to culture, their need of being grown in a host cell makes it difficult to obtain large amounts of organism-specific DNA necessary for whole genome sequencing. [2] The first complete genome sequencing was done on A. Marginale St. Maries strain.
Members of the order Rickettsiales are small, obligate intracellular bacteria that typically have short genomes due to possibly "reductive evolution" as endosymbionts. Because many obligate bacteria are difficult to culture ''in vitro'', the need of a host for growth makes it difficult to obtain large amounts of the organism-specific DNA necessary for whole genome sequencing [2]. The first complete genome sequencing was done on the St. Maries strain:


*Genes: 1005
*Genes: 1005
Line 64: Line 71:


==Cell structure and metabolism==
==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'' undergoes anaerobic glycolysis in the cytosol.  In vitro tests on organism substrates has shown to use pyruvate, a glycolytic product, for its metabolism.
''Anaplasma marginale'' is a pathogenic gram-negative stain bacteria with an outer membrane composed of lipopolysaccharides.  Interestingly, several genes for lipopolysaccharide and lipid A biosyntheses are missing [2].  A complete pathway for peptidoglycan synthesis was also not present. "The lack of a traditional cell wall seems to be a common feature for the family Anaplasmataceae, but not from the order Rickettsiales because the family Rickettsiaceae are capable of synthesizing lipopolysaccharide and peptidoglycan. Unlike other members of the family, ''A. marginale'' does not seem to be particularly fragile, and may be able to strengthen its cell in an alternative way."
 
For energy, ''Anaplasma marginale'' undergoes aerobic respiration using the TCA cycle. Anaerobic metabolism, glycolysis, occurs in its cytosol. In vitro tests on organism substrates have shown the use of pyruvate, a glycolytic product, for its metabolism [3]. Even though most of the glycolytic enzymes were detected, a sugar transport system was not found; therefore, the organism may depend more heavily on gluconeogenesis for its glucose supply [2].
 
Members of its class, Alphaproteobacteria and particularly from the order Rickettsiales, are thought to be the precursors of eukaryotic cell mitochondria. According to the endosymbiotic theory, the mitochondria organelle now existent in eukaryotic cells originated as separate prokaryotic organisms, which were taken inside the cell as endosymbionts [4].


==Ecology==
==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.
''Anaplasma marginale'' is endemic to topical and subtropical regions of the world. Its greatest ecological impact prevails as a worldwide livestock pathogen that impacts animal health and concomitant economic health.   


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==
==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.
''A. marginale'' is the most pathogenic of its species causing anaplasmosis, which is a form of tick fever carried by specific cattle tick species. The pathogen multiplies within the tick and can be pass to later stages of the tick's life cycle, but the infection is not passed to the eggs. As carriers, ticks are unaffected by the bacteria; they infect cattle by feeding off the blood of a 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 [7].
 
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==
The disease begins its course by invading and multiplying within red blood cells of the host (i.e. cattle). The gram-negative bacteria produce endotoxins through its lipopolysaccharide outer membrane. As the disease progresses, infected and even uninfected red blood cells are destroyed predominantly in the liver and spleen, resulting in increasing anemia and, in severe cases, death of the host. [7]
''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==
Clinical symptoms of infection:
'''"Identification of midgut and salivary glands as specific and distinct barriers to efficient tick-borne transmission of Anaplasma marginale."'''
* Transient fever
* Weakness
* Respiratory distress particularly after physical exertions
* Depression
* Loss of appetite
* Jaundice
* Brown urine due to bile pigments


Ueti MW, Reagan JO Jr, Knowles DP Jr, Scoles GA, Shkap V, Palmer GH.
Cattle that recover from anaplasmosis remain carriers of the organism but are immune to further disease. Calves from immune mothers receive maternal antibodies against ''A. marginale'' from milk.  These calves eventually also develop a lasting immunity; therefore, it is possible to have both ''Anaplasma marginale'' and cattle ticks present in a livestock environment without fear of serious infection outbreaks [7].
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.
==Application to Biotechnology==
 
 
 
'''"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.


Studies conducted in this organism aim at finding vaccines against the bacteria and its relatives of the order Rickettsiales, which are pathogens for both animals and humans.


==Current Research==
Because of its damaging, pathogenic nature, much of the current research on this organism is on finding effective vaccines against ''Anaplasma marginale'' and its relatives.


'''"Outer Membrane Protein Complex of Anaplasma Marginale, Use in Vaccine Development Through Genomics"'''
For efficient tick-borne transmission of the bacteria, there are at least two specific barriers, the midgut and salivary glands. “An inability to colonize the midgut epithelium prevents subsequent development within the salivary glands and thus prevents transmission of the ''A. Marginale'' to the host.” [8] Understanding the complexity of the pathogen-tick interaction can open up novel methods of preventing infections.


Scoles, G., Palmer, G.
“Within the mammalian host, the bacteria generate antigenic variants by changing a surface coat composed of numerous proteins… the surface coat is dominated by two families containing immunodominant proteins: the msp2 superfamily and the msp1 superfamily” [2]. Membrane surface proteins can be useful as microbial identifiers and therefore act as antigens eliciting an immune response.  Safe vaccine possibilities currently include testing if recombinant major surface protein antigens will produce an effective immune response to protect the animal from future infections [9].  
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.
To add to the difficulty of creating an effective vaccine, the USDA Agriculture Research Service is currently studying the outer membrane protein complex of ''Anaplasma marginale'' that includes protection-inducing proteins.  The recombinant-based vaccine would be more effective at targeting this cattle disease as it takes into account possible protection mechanisms of the organism [10].


==References==
==References==

Latest revision as of 19:55, 25 May 2011

This is a curated page. Report corrections to Microbewiki.

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

Anaplasma marginale is the most prevalent tick-borne, livestock pathogen worldwide and poses a considerable constraint to animal health. The disease results in significant morbidity and mortality of United State's (US) cattle population, which affects the exportation of beef. Despite a global impact on animal health, there is no widely accepted vaccine for "Anaplasma marginale." Live vaccinations are blood-based and are often used in tropical countries, but they cannot be licensed in the U.S. because of the risk of transmitting any known or unknown pathogens [1]. Thus, finding an effective vaccine for anaplasmosis is a priority for the USDA National Cattlemen’s Beef Association and many other research groups.

'The genus Anaplasma which contains both animal and human pathogens. Being a Rickettsiales obligate intracellular bacterium, it requires a host in order survive. These organisms can be easily cultured from the red blood cells of cattle. While mammalian erythrocytes seem to be the only site of infection, the bacterium also undergoes a complex developmental cycle in ticks. When a tick feeds on a host cattle, the bacteria enter through the site of the bite, infecting the animal. The genomic information of the species would have a broad applicability to closely related organisms within the same order, since members of Rickettsiales 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 short genomes due to possibly "reductive evolution" as endosymbionts. Because many obligate bacteria are difficult to culture in vitro, the need of a host for growth makes it difficult to obtain large amounts of the organism-specific DNA necessary for whole genome sequencing [2]. The first complete genome sequencing was done on the 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

[5,6]

Cell structure and metabolism

Anaplasma marginale is a pathogenic gram-negative stain bacteria with an outer membrane composed of lipopolysaccharides. Interestingly, several genes for lipopolysaccharide and lipid A biosyntheses are missing [2]. A complete pathway for peptidoglycan synthesis was also not present. "The lack of a traditional cell wall seems to be a common feature for the family Anaplasmataceae, but not from the order Rickettsiales because the family Rickettsiaceae are capable of synthesizing lipopolysaccharide and peptidoglycan. Unlike other members of the family, A. marginale does not seem to be particularly fragile, and may be able to strengthen its cell in an alternative way."

For energy, Anaplasma marginale undergoes aerobic respiration using the TCA cycle. Anaerobic metabolism, glycolysis, occurs in its cytosol. In vitro tests on organism substrates have shown the use of pyruvate, a glycolytic product, for its metabolism [3]. Even though most of the glycolytic enzymes were detected, a sugar transport system was not found; therefore, the organism may depend more heavily on gluconeogenesis for its glucose supply [2].

Members of its class, Alphaproteobacteria and particularly from the order Rickettsiales, are thought to be the precursors of eukaryotic cell mitochondria. According to the endosymbiotic theory, the mitochondria organelle now existent in eukaryotic cells originated as separate prokaryotic organisms, which were taken inside the cell as endosymbionts [4].

Ecology

Anaplasma marginale is endemic to topical and subtropical regions of the world. Its greatest ecological impact prevails as a worldwide livestock pathogen that impacts animal health and concomitant economic health.


Pathology

A. marginale is the most pathogenic of its species causing anaplasmosis, which is a form of tick fever carried by specific cattle tick species. The pathogen multiplies within the tick and can be pass to later stages of the tick's life cycle, but the infection is not passed to the eggs. As carriers, ticks are unaffected by the bacteria; they infect cattle by feeding off the blood of a 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 [7].

The disease begins its course by invading and multiplying within red blood cells of the host (i.e. cattle). The gram-negative bacteria produce endotoxins through its lipopolysaccharide outer membrane. As the disease progresses, infected and even uninfected red blood cells are destroyed predominantly in the liver and spleen, resulting in increasing anemia and, in severe cases, death of the host. [7]

Clinical symptoms of infection:

  • Transient fever
  • Weakness
  • Respiratory distress particularly after physical exertions
  • Depression
  • Loss of appetite
  • Jaundice
  • Brown urine due to bile pigments

Cattle that recover from anaplasmosis remain carriers of the organism but are immune to further disease. Calves from immune mothers receive maternal antibodies against A. marginale from milk. These calves eventually also develop a lasting immunity; therefore, it is possible to have both Anaplasma marginale and cattle ticks present in a livestock environment without fear of serious infection outbreaks [7].

Application to Biotechnology

Studies conducted in this organism aim at finding vaccines against the bacteria and its relatives of the order Rickettsiales, which are pathogens for both animals and humans.

Current Research

Because of its damaging, pathogenic nature, much of the current research on this organism is on finding effective vaccines against Anaplasma marginale and its relatives.

For efficient tick-borne transmission of the bacteria, there are at least two specific barriers, the midgut and salivary glands. “An inability to colonize the midgut epithelium prevents subsequent development within the salivary glands and thus prevents transmission of the A. Marginale to the host.” [8] Understanding the complexity of the pathogen-tick interaction can open up novel methods of preventing infections.

“Within the mammalian host, the bacteria generate antigenic variants by changing a surface coat composed of numerous proteins… the surface coat is dominated by two families containing immunodominant proteins: the msp2 superfamily and the msp1 superfamily” [2]. Membrane surface proteins can be useful as microbial identifiers and therefore act as antigens eliciting an immune response. Safe vaccine possibilities currently include testing if recombinant major surface protein antigens will produce an effective immune response to protect the animal from future infections [9].

To add to the difficulty of creating an effective vaccine, the USDA Agriculture Research Service is currently studying the outer membrane protein complex of Anaplasma marginale that includes protection-inducing proteins. The recombinant-based vaccine would be more effective at targeting this cattle disease as it takes into account possible protection mechanisms of the organism [10].

References

1) Kocan K.M., de la Fuente J., Guglielmone A.A., Melendez RD. “Antigens and alternatives for control of Anaplasma marginale infection in cattle”. Clinical Microbiology Reviews. 2003 Oct. 16, Vol 4. p. 698-712.

2) 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 Nov. Vol 102. p 844-9.

3) 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.

4) Margulis, Lynn, “Serial endosymbiotic theory (SET) and composite individuality – Transition from bacterial to eukaryotic genomes.” Microbiology Today. 2004 Nov. Vol 31. p 172-174.

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

6) TGR-CMR, "Anaplasma marginale St. Maries Genome" Retrieved 1 May, 2007

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

8) 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.

9) Kawasaki PM, Kano FS, Tamekuni K, Garcia JL, Marana ER, Vidotto O, Vidotto MC. “Immune response of BALB/c mouse immunized with recombinant MSPs proteins of Anaplasma marginale binding to immunostimulant complex (ISCOM)”. Res Vet Sci. 2007 Mar. 27.

10) USDA, “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


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

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