Anaplasma phagocytophilum: Difference between revisions
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==Description and significance== | ==Description and significance== | ||
Anaplasma phagocytophilum is an intracellular obligate pathogen. It is widely distributed and can be found in North America, Europe, and Asia. Anaplasma phagocytophilum causes the disease | ''Anaplasma phagocytophilum''is an intracellular obligate pathogen. It is widely distributed and can be found in North America, Europe, and Asia. ''Anaplasma phagocytophilum'' causes the disease human granulocytic ehrlichiosis(HGE) and is most often spread through tick bites and is thus widely studied. The bacterium infects and colonizes neutrophils in host organisms, often leading to immunodeficiency diseases(1). | ||
The | The human granulocytic ehrlichiosis pathogen was first described in 1994 in patients in Wisconsin and Minnesota(14). Ticks collected from the area of infection were also discovered to be carriers of the HGE pathogen(14). The infectious agent, first classified as ''Ehrlichia phagocytophila'' has recently been reclassified as ''Anaplasma phagocytophilum''(14). | ||
==Genome structure== | ==Genome structure== | ||
Anaplasma phagocytophilum has one circular genome composed of 1471282 base pairs, composing 1264 protein genes (4). Anaplasma phagocytophilum contains no known plasmids (8). | ''Anaplasma phagocytophilum'' has one circular genome composed of 1471282 base pairs, composing 1264 protein genes (4). ''Anaplasma phagocytophilum'' contains no known plasmids (8). | ||
==Cell structure and metabolism== | ==Cell structure and metabolism== | ||
Anaplasma phagocytophilum is a small gram negative bacterium of 0.2-2 micrometer diameter(5). It is a obligate intracellular pathogen and replicates within a host cell vacuole to form a morula microcolony(5). On the membrane surface of Anaplasma phagocytophilum can be found its major antigenic membrane proteins p44 and msp2 both of which are approximately 44-kDa in size(13). These two membrane proteins play a vital role in | ''Anaplasma phagocytophilum'' is a small gram-negative bacterium of 0.2-2 micrometer diameter(5). It is a obligate intracellular pathogen and replicates within a host cell vacuole to form a morula microcolony(5). On the membrane surface of ''Anaplasma phagocytophilum'' can be found its major antigenic membrane proteins, p44 and msp2, both of which are approximately 44-kDa in size(13). These two membrane proteins play a vital role in ''Anaplasma phagocytophilum'' virulence. The bacterium has a Type-IV secretion apparatus by which it is able to transfer materials between itself and the host(12). | ||
Unlike many gram negative | Unlike many gram-negative bacteria, ''Anaplasma phagocytophilum'' lacks a peptidoglycan layer on its outer membrane(7). In addition, it lacks the genes necessary for the biosynthesis of lipid A and peptidoglycan, resulting in very fragile cells that are highly susceptible to stress(7). | ||
Anaplasma phagocytophilum is a disease causing intracellular bacterium in dogs, humans, horses and ruminants(3). It lacks lipopolysaccharide biosynthetic machinery(12). The | ''Anaplasma phagocytophilum'' is a disease causing intracellular bacterium in dogs, humans, horses and ruminants(3). It lacks lipopolysaccharide biosynthetic machinery(12). The bacteria reside in host endosomes whereby they obtain the nutrients sufficient to carry out binary fission(12). | ||
Due to the lack of the ability to synthesize peptidoglycan, Anaplasma phagocytophilum | Due to the lack of the ability to synthesize peptidoglycan, ''Anaplasma phagocytophilum'' relies on membrane cholesterol to maintain physical integrity(7). ''Anaplasma phagocytophilum'' also lacks genes related to the biosynthesis or modification of cholesterol or related sterols(7). All cholesterols are therefore are directly taken from exogenous sources without extensive modification before incorporation into the membrane(7). | ||
Anaplasma phagocytophilum is able to carry out major metabolic pathways including glycolysis, citric acid cycle | ''Anaplasma phagocytophilum'' is able to carry out major metabolic pathways including glycolysis, the citric acid cycle and the pentose phosphate pathway(16). It is able to metabolize saccharides such as pentose, fructose and mannose into metabolic intermediates(16). | ||
==Ecology== | ==Ecology== | ||
Anaplasma phagocytophilum is distributed widely throughout vast geographical regions. In North America, it is most common in the north-east, upper Midwest and northern California in the United States(5). It is also discovered in several European and Asian countries(1). It is prevalent in regions with tropical to sub-trophical climate (10). Anaplasma phagocytophilum can be successfully cultured at 37 degrees Celcius(Park). The primary host of Anaplasma phagocytophilum in North America is the white-footed mouse with human beings as merely accidental hosts(9). A wide range of mammals such as horses, cows, and | ''Anaplasma phagocytophilum'' is distributed widely throughout vast geographical regions. In North America, it is most common in the north-east, upper Midwest and northern California in the United States(5). It is also discovered in several European and Asian countries(1). It is prevalent in regions with tropical to sub-trophical climate (10). ''Anaplasma phagocytophilum'' can be successfully cultured at 37 degrees Celcius(Park). The primary host of ''Anaplasma phagocytophilum'' in North America is the white-footed mouse with human beings as merely accidental hosts(9). A wide range of mammals such as horses, cows, and sheep can serve as host for the bacterium(5). | ||
==Pathology== | ==Pathology== | ||
Anaplasma phagocytophilum is the cause of Human granulocytic ehrlichiosis. This is a prevalent human tickborne zoonosis of the neutrophils (1). The pathogen persists within the polymorphonuclear leucocytes(1). The disease was first identified in 1990 in a patient in Wisconsin (1). | ''Anaplasma phagocytophilum'' is the cause of Human granulocytic ehrlichiosis. This is a prevalent human tickborne zoonosis of the neutrophils (1). The pathogen persists within the polymorphonuclear leucocytes(1). The disease was first identified in 1990 in a patient in Wisconsin (1). | ||
Anaplasma phagocytophilum infection in humans | ''Anaplasma phagocytophilum'' infection in humans delays the onset of apoptosis in neutrophils, allowing for more effective infections of the neutrophils(5). ''Anaplasma phagocytophilum'' also causes an increase in IL-8, a neutrophil chemoattractant that increases the phagocytosis of neutrophils. Studies suggest that this is to increase bacterium dissemination into neutrophils(5). These permutations to the neutrophils can lead to immunological changes, making the host more susceptible to opportunistic infections(1). | ||
Human granulocytic anaplasmosis is characterized by, but not limited to, symptoms of malaise, fever, myalgia, | Human granulocytic anaplasmosis is characterized by, but not limited to, symptoms of malaise, fever, myalgia, headache, gastrointestinal tract involvement (nausea, vomiting, diarrhea) and involvement of the respiratory tract (cough, pulmonary infiltrates) (1). Other injuries to the body sometimes include skin rash, leukopenia, thrombocytopenia, and damage to the liver(1). | ||
Anaplasma phagocytophilum also causes ehrlichiosis in other species including domesticated animals such as horses, | ''Anaplasma phagocytophilum'' also causes ehrlichiosis in other species including domesticated animals such as horses, sheep, and cattle (10). Similar to human granulocytic anaplasmosis, these forms of anaplasmosis are caused by the bacterium transmitted via tick bites (10). | ||
==Application to Biotechnology== | ==Application to Biotechnology== | ||
Due to its obligate intracellular pathogenic nature, Anaplasma phagocytophilum is not an ideal target for mutagenesis techniques(8). A widespread method for genetic transformation of Anaplasma phagocytophilum is currently | Due to its obligate intracellular pathogenic nature, ''Anaplasma phagocytophilum'' is not an ideal target for mutagenesis techniques(8). A widespread method for genetic transformation of ''Anaplasma phagocytophilum'' is currently unavailable due to various factors. Factors that contribute to this include difficulties in returning transformed bacteria populations into host cells, selection via antibiotics, and obtaining high efficiency of homologous recombination(8). Because of this difficulty, ''Anaplasma phagocytophilum ''is not widely used for the production of enzymes and compounds. | ||
==Current Research== | ==Current Research== | ||
Currently research is being conducted with regards to the AnkA gene in | Currently research is being conducted with regards to the AnkA gene in ''Anaplasma phagocytophilum''. AnkA is a 153-160kDa protein with 11 N-terminal ankyrin repeats and a C-terminus with several tandem repeats(17). Currently, AnkA is the only protein that is known to be secreted by ''Anaplasma phagocytophilum'' and is believed to be instrumental in the infection of neutrophils. It is hypothesized that AnkA leaves the bacterium via its type IV secretion apparatus and binds to the nuclear proteins of neutrophils(17). AnkA varies among different strains of ''Anaplasma phagocytophilum'' although different populations maintain regions of conservation(17). Currently, the effect of geological variation of AnkA on its function is unknown | ||
Research is also conducted into the methods with which Anaplasma phagocytophilum resists the immune system. The primary method with which neutrophils attack pathogens is via the superoxide anion, produced by the NADPH oxidase complex(15). However, once within the host cell, Anaplasma phagocytophilum rapidly | Research is also conducted into the methods with which ''Anaplasma phagocytophilum'' resists the immune system. The primary method with which neutrophils attack pathogens is via the superoxide anion, produced by the NADPH oxidase complex(15). However, once within the host cell, ''Anaplasma phagocytophilum'' rapidly detoxifies the superoxide via a still unknown method and resides within a protective vacuole that segregates it from superoxide anions(15). The mechanism of superoxide anion resistance remains to be discovered. | ||
Research is also conducted in the area of serological interaction between Anaplasma phagocytophilum and Anaplasma marginale. It is noted that in | Research is also conducted in the area of serological interaction between ''Anaplasma phagocytophilum'' and ''Anaplasma marginale''. It is noted that in cattle and horses exposed to ''Anaplasma marginale'', antibodies to ''A. phagocytophilum'' were also produced(10). Conversely, cattle and horses exposed to ''A. phagocytophilum'' also produce antibodies to ''A. marginale''(10). Thus, currently serological testing methods are presently under evaluation as they lack specificity. | ||
==References== | ==References== | ||
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10. U. M. Dreher. 2005. “Serologic Cross-Reactivity between Anaplasma marginale and Anaplasma phagocytophilum”. Clin Diagn Lab Immunol. 2005 October; 12(10): 1177–1183. | 10. U. M. Dreher. 2005. “Serologic Cross-Reactivity between Anaplasma marginale and Anaplasma phagocytophilum”. Clin Diagn Lab Immunol. 2005 October; 12(10): 1177–1183. | ||
11. Pathogenesis of A. phagocytophilum Infections. 2005. Medscape | 11. Pathogenesis of A. phagocytophilum Infections. 2005. Emerg Infect Dis. Medscape | ||
12. Bakken, Johan S. 2005. “Human granulocytic anaplasmosis and Anaplasma phagocytophilum”. Emerging Infectious Diseases 2005/12/1 | 12. Bakken, Johan S. 2005. “Human granulocytic anaplasmosis and Anaplasma phagocytophilum”. Emerging Infectious Diseases 2005/12/1 | ||
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14. Holman, Mary S. 2004. “Anaplasma phagocytophilum, Babesia microti, and Borrelia burgdorferi in Ixodes scapularis, Southern Coastal Maine”. Emerging Infectious Diseases. Vol. 10, No. 4 April 2004 | 14. Holman, Mary S. 2004. “Anaplasma phagocytophilum, Babesia microti, and Borrelia burgdorferi in Ixodes scapularis, Southern Coastal Maine”. Emerging Infectious Diseases. Vol. 10, No. 4 April 2004 | ||
15. Carlyon, Jason A. 2006. | 15. Carlyon, Jason A. 2006. “phagocytophilum adhesins that facilitate attachment to neutrophils”. Department of Microbiology, Immunology and Molecular Genetics. University of Kentucky. May 2006 | ||
Latest revision as of 15:26, 2 June 2011
A Microbial Biorealm page on the genus Anaplasma phagocytophilum
Classification
Higher order taxa
Bacteria; proteabacteria; alphaproteobacteria; rickettsiales; anaplasmataceae; Anaplasma; phagocytophium group (2)
Species
|
NCBI: Taxonomy |
Anaplasma phagocytophilum; Anaplasma marginale; Anaplasma platys(2)
Description and significance
Anaplasma phagocytophilumis an intracellular obligate pathogen. It is widely distributed and can be found in North America, Europe, and Asia. Anaplasma phagocytophilum causes the disease human granulocytic ehrlichiosis(HGE) and is most often spread through tick bites and is thus widely studied. The bacterium infects and colonizes neutrophils in host organisms, often leading to immunodeficiency diseases(1). The human granulocytic ehrlichiosis pathogen was first described in 1994 in patients in Wisconsin and Minnesota(14). Ticks collected from the area of infection were also discovered to be carriers of the HGE pathogen(14). The infectious agent, first classified as Ehrlichia phagocytophila has recently been reclassified as Anaplasma phagocytophilum(14).
Genome structure
Anaplasma phagocytophilum has one circular genome composed of 1471282 base pairs, composing 1264 protein genes (4). Anaplasma phagocytophilum contains no known plasmids (8).
Cell structure and metabolism
Anaplasma phagocytophilum is a small gram-negative bacterium of 0.2-2 micrometer diameter(5). It is a obligate intracellular pathogen and replicates within a host cell vacuole to form a morula microcolony(5). On the membrane surface of Anaplasma phagocytophilum can be found its major antigenic membrane proteins, p44 and msp2, both of which are approximately 44-kDa in size(13). These two membrane proteins play a vital role in Anaplasma phagocytophilum virulence. The bacterium has a Type-IV secretion apparatus by which it is able to transfer materials between itself and the host(12). Unlike many gram-negative bacteria, Anaplasma phagocytophilum lacks a peptidoglycan layer on its outer membrane(7). In addition, it lacks the genes necessary for the biosynthesis of lipid A and peptidoglycan, resulting in very fragile cells that are highly susceptible to stress(7). Anaplasma phagocytophilum is a disease causing intracellular bacterium in dogs, humans, horses and ruminants(3). It lacks lipopolysaccharide biosynthetic machinery(12). The bacteria reside in host endosomes whereby they obtain the nutrients sufficient to carry out binary fission(12). Due to the lack of the ability to synthesize peptidoglycan, Anaplasma phagocytophilum relies on membrane cholesterol to maintain physical integrity(7). Anaplasma phagocytophilum also lacks genes related to the biosynthesis or modification of cholesterol or related sterols(7). All cholesterols are therefore are directly taken from exogenous sources without extensive modification before incorporation into the membrane(7). Anaplasma phagocytophilum is able to carry out major metabolic pathways including glycolysis, the citric acid cycle and the pentose phosphate pathway(16). It is able to metabolize saccharides such as pentose, fructose and mannose into metabolic intermediates(16).
Ecology
Anaplasma phagocytophilum is distributed widely throughout vast geographical regions. In North America, it is most common in the north-east, upper Midwest and northern California in the United States(5). It is also discovered in several European and Asian countries(1). It is prevalent in regions with tropical to sub-trophical climate (10). Anaplasma phagocytophilum can be successfully cultured at 37 degrees Celcius(Park). The primary host of Anaplasma phagocytophilum in North America is the white-footed mouse with human beings as merely accidental hosts(9). A wide range of mammals such as horses, cows, and sheep can serve as host for the bacterium(5).
Pathology
Anaplasma phagocytophilum is the cause of Human granulocytic ehrlichiosis. This is a prevalent human tickborne zoonosis of the neutrophils (1). The pathogen persists within the polymorphonuclear leucocytes(1). The disease was first identified in 1990 in a patient in Wisconsin (1). Anaplasma phagocytophilum infection in humans delays the onset of apoptosis in neutrophils, allowing for more effective infections of the neutrophils(5). Anaplasma phagocytophilum also causes an increase in IL-8, a neutrophil chemoattractant that increases the phagocytosis of neutrophils. Studies suggest that this is to increase bacterium dissemination into neutrophils(5). These permutations to the neutrophils can lead to immunological changes, making the host more susceptible to opportunistic infections(1). Human granulocytic anaplasmosis is characterized by, but not limited to, symptoms of malaise, fever, myalgia, headache, gastrointestinal tract involvement (nausea, vomiting, diarrhea) and involvement of the respiratory tract (cough, pulmonary infiltrates) (1). Other injuries to the body sometimes include skin rash, leukopenia, thrombocytopenia, and damage to the liver(1). Anaplasma phagocytophilum also causes ehrlichiosis in other species including domesticated animals such as horses, sheep, and cattle (10). Similar to human granulocytic anaplasmosis, these forms of anaplasmosis are caused by the bacterium transmitted via tick bites (10).
Application to Biotechnology
Due to its obligate intracellular pathogenic nature, Anaplasma phagocytophilum is not an ideal target for mutagenesis techniques(8). A widespread method for genetic transformation of Anaplasma phagocytophilum is currently unavailable due to various factors. Factors that contribute to this include difficulties in returning transformed bacteria populations into host cells, selection via antibiotics, and obtaining high efficiency of homologous recombination(8). Because of this difficulty, Anaplasma phagocytophilum is not widely used for the production of enzymes and compounds.
Current Research
Currently research is being conducted with regards to the AnkA gene in Anaplasma phagocytophilum. AnkA is a 153-160kDa protein with 11 N-terminal ankyrin repeats and a C-terminus with several tandem repeats(17). Currently, AnkA is the only protein that is known to be secreted by Anaplasma phagocytophilum and is believed to be instrumental in the infection of neutrophils. It is hypothesized that AnkA leaves the bacterium via its type IV secretion apparatus and binds to the nuclear proteins of neutrophils(17). AnkA varies among different strains of Anaplasma phagocytophilum although different populations maintain regions of conservation(17). Currently, the effect of geological variation of AnkA on its function is unknown Research is also conducted into the methods with which Anaplasma phagocytophilum resists the immune system. The primary method with which neutrophils attack pathogens is via the superoxide anion, produced by the NADPH oxidase complex(15). However, once within the host cell, Anaplasma phagocytophilum rapidly detoxifies the superoxide via a still unknown method and resides within a protective vacuole that segregates it from superoxide anions(15). The mechanism of superoxide anion resistance remains to be discovered. Research is also conducted in the area of serological interaction between Anaplasma phagocytophilum and Anaplasma marginale. It is noted that in cattle and horses exposed to Anaplasma marginale, antibodies to A. phagocytophilum were also produced(10). Conversely, cattle and horses exposed to A. phagocytophilum also produce antibodies to A. marginale(10). Thus, currently serological testing methods are presently under evaluation as they lack specificity.
References
1. J. Stephen Dumler; Kyoung-Seong Choi. 2005. “Human Granulocytic Anaplasmosis and Anaplasma phagocytophilum”. Medscape 2005 December 27.
2. Anaplasma phagocytophilum HZ Genome Page; http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?org=gaph
3. J. S. Dumler, K. M. Asanovich, and J. S. Bakken. 2003.”Analysis of Genetic Identity of North American Anaplasma phagocytophilum Strains by Pulsed-Field Gel Electrophoresis”. J Clin Microbiol. 2003 July; 41(7): 3392–3394.
4. Anaplasma phagocytophilum Genome map browser. http://www.genome.jp/kegg-bin/show_genomemap_top?org_id=aph
5. Thomas V, Fikrig E. 2007 “Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection”. Cell Microbiol 2007 March 8
6..Jason A. Carlyon and Erol Fikrig. 2003. “Invasion and survival strategies of Anaplasma phagocytophilum”. Cellular Microbiology. Volume 5 Issue 11 Page 743 - November 2003
7. Mingqun Lin and Yasuko Rikihisa. 2003. “Ehrlichia chaffeensis and Anaplasma phagocytophilum Lack Genes for Lipid A Biosynthesis and Incorporate Cholesterol for Their Survival”. Infection and Immunity, September 2003, p. 5324-5331, Vol. 71, No. 9
8. Felsheim. Roderick F. 2006. “Transformation of Anaplasma phagocytophilum”. BMC Biotechnology 2006, 6:42 doi:10.1186/1472-6750-6-42
9. Jinho Park. 2003. “Major Surface Protein 2 of Anaplasma phagocytophilum Facilitates Adherence to Granulocytes”. Infect Immun. 2003 July; 71(7): 4018–4025.
10. U. M. Dreher. 2005. “Serologic Cross-Reactivity between Anaplasma marginale and Anaplasma phagocytophilum”. Clin Diagn Lab Immunol. 2005 October; 12(10): 1177–1183.
11. Pathogenesis of A. phagocytophilum Infections. 2005. Emerg Infect Dis. Medscape
12. Bakken, Johan S. 2005. “Human granulocytic anaplasmosis and Anaplasma phagocytophilum”. Emerging Infectious Diseases 2005/12/1
13. Quan Lin. 2006. “Analysis of Involvement of the RecF Pathway in p44 Recombination in Anaplasma phagocytophilum and in Escherichia coli by Using a Plasmid Carrying the p44 Expression and p44 Donor Loci”. Infection and Immunity, April 2006, p. 2052-2062, Vol. 74, No. 4
14. Holman, Mary S. 2004. “Anaplasma phagocytophilum, Babesia microti, and Borrelia burgdorferi in Ixodes scapularis, Southern Coastal Maine”. Emerging Infectious Diseases. Vol. 10, No. 4 April 2004
15. Carlyon, Jason A. 2006. “phagocytophilum adhesins that facilitate attachment to neutrophils”. Department of Microbiology, Immunology and Molecular Genetics. University of Kentucky. May 2006
