Biology of ehrlichiae
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
- J Stephen Dumler, MD
J Stephen Dumler, MD
- Professor and Chair
- Department of Pathology
- Uniformed Services University of the Health Sciences
- Walter Reed National Military Medical Center
- Joint Pathology Center
Ehrlichiae, which include bacteria in the family Anaplasmataceae, have been known to cause diseases of interest to veterinarians for over 100 years. However, their role as agents of human disease was not recognized until 1987. Since then, the number of ehrlichiae recognized to cause human disease has rapidly expanded, as has our knowledge about the epidemiology, clinical characteristics, and treatment of the diseases caused by these organisms.
The biology of ehrlichiae will be reviewed in this topic. A discussion of the diseases caused by these bacteria is presented separately. (See "Human ehrlichiosis and anaplasmosis".)
TAXONOMY AND PHYLOGENY
The taxonomy of the Rickettsiales order and the two major families (Rickettsiaceae and Anaplasmataceae) underwent a radical change during the last two decades [1,2], based mostly on genomic data, but also on phenotypic features. A detailed discussion of Rickettsiaceae is presented separately. (See "Biology of Rickettsia rickettsii infection".)
The current configuration of the genus Anaplasmataceae provides for four to five clades that represent individual genera: Ehrlichia, Anaplasma, Neoehrlichia, Neorickettsia, and Wolbachia. These Anaplasmataceae can be divided into tick and non-tick transmitted bacteria:
●Tick-transmitted – All members of the genera Ehrlichia, Anaplasma, and Neoehrlichia are transmitted by the bites of ticks. These include:
- Dumler JS, Rikihisa Y, Dasch GA. Genus I. Anaplasma. In: Bergey's Manual of Systematic Bacteriology, 2, Garrity GM, Brenner DJ, Krieg NR, Staley JT (Eds), Springer, East Lansing 2005. Vol 2, p.117.
- Dumler JS, Walker DH. Order II: Rickettsiales. In: Bergey's Manual of Systematic Bacteriology, 2, Garrity GM, Brenner DJ, Krieg NR, Staley JT (Eds), Springer, New York 2005. Vol 2, p.96.
- Slatko BE, Luck AN, Dobson SL, Foster JM. Wolbachia endosymbionts and human disease control. Mol Biochem Parasitol 2014; 195:88.
- Dunning Hotopp JC, Lin M, Madupu R, et al. Comparative genomics of emerging human ehrlichiosis agents. PLoS Genet 2006; 2:e21.
- Zhu B, Kuriakose JA, Luo T, et al. Ehrlichia chaffeensis TRP120 binds a G+C-rich motif in host cell DNA and exhibits eukaryotic transcriptional activator function. Infect Immun 2011; 79:4370.
- Rennoll-Bankert KE, Garcia-Garcia JC, Sinclair SH, Dumler JS. Chromatin-bound bacterial effector ankyrin A recruits histone deacetylase 1 and modifies host gene expression. Cell Microbiol 2015; 17:1640.
- Troese MJ, Kahlon A, Ragland SA, et al. Proteomic analysis of Anaplasma phagocytophilum during infection of human myeloid cells identifies a protein that is pronouncedly upregulated on the infectious dense-cored cell. Infect Immun 2011; 79:4696.
- Zhang JZ, Popov VL, Gao S, et al. The developmental cycle of Ehrlichia chaffeensis in vertebrate cells. Cell Microbiol 2007; 9:610.
- McKechnie DB, Slater KS, Childs JE, et al. Survival of Ehrlichia chaffeensis in refrigerated, ADSOL-treated RBCs. Transfusion 2000; 40:1041.
- Kalantarpour F, Chowdhury I, Wormser GP, Aguero-Rosenfeld ME. Survival of the human granulocytic ehrlichiosis agent under refrigeration conditions. J Clin Microbiol 2000; 38:2398.
- Rikihisa Y. Molecular events involved in cellular invasion by Ehrlichia chaffeensis and Anaplasma phagocytophilum. Vet Parasitol 2010; 167:155.
- Truchan HK, Seidman D, Carlyon JA. Breaking in and grabbing a meal: Anaplasma phagocytophilum cellular invasion, nutrient acquisition, and promising tools for their study. Microbes Infect 2013; 15:1017.
- Garcia-Garcia JC, Rennoll-Bankert KE, Pelly S, et al. Silencing of host cell CYBB gene expression by the nuclear effector AnkA of the intracellular pathogen Anaplasma phagocytophilum. Infect Immun 2009; 77:2385.
- Sinclair SH, Rennoll-Bankert KE, Dumler JS. Effector bottleneck: microbial reprogramming of parasitized host cell transcription by epigenetic remodeling of chromatin structure. Front Genet 2014; 5:274.
- Rennoll-Bankert KE, Dumler JS. Lessons from Anaplasma phagocytophilum: chromatin remodeling by bacterial effectors. Infect Disord Drug Targets 2012; 12:380.
- Singu V, Liu H, Cheng C, Ganta RR. Ehrlichia chaffeensis expresses macrophage- and tick cell-specific 28-kilodalton outer membrane proteins. Infect Immun 2005; 73:79.
- Scorpio DG, Leutenegger C, Berger J, et al. Sequential analysis of Anaplasma phagocytophilum msp2 transcription in murine and equine models of human granulocytic anaplasmosis. Clin Vaccine Immunol 2008; 15:418.
- Chen SM, Dumler JS, Bakken JS, Walker DH. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J Clin Microbiol 1994; 32:589.
- Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275:199.
- Goodman JL, Nelson C, Vitale B, et al. Direct cultivation of the causative agent of human granulocytic ehrlichiosis. N Engl J Med 1996; 334:209.
- Buller RS, Arens M, Hmiel SP, et al. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N Engl J Med 1999; 341:148.
- Fishbein DB, Sawyer LA, Holland CJ, et al. Unexplained febrile illnesses after exposure to ticks. Infection with an Ehrlichia? JAMA 1987; 257:3100.
- Dumler JS, Dawson JE, Walker DH. Human ehrlichiosis: hematopathology and immunohistologic detection of Ehrlichia chaffeensis. Hum Pathol 1993; 24:391.
- Herron MJ, Nelson CM, Larson J, et al. Intracellular parasitism by the human granulocytic ehrlichiosis bacterium through the P-selectin ligand, PSGL-1. Science 2000; 288:1653.
- Seidman D, Hebert KS, Truchan HK, et al. Essential domains of Anaplasma phagocytophilum invasins utilized to infect mammalian host cells. PLoS Pathog 2015; 11:e1004669.
- Lin M, den Dulk-Ras A, Hooykaas PJ, Rikihisa Y. Anaplasma phagocytophilum AnkA secreted by type IV secretion system is tyrosine phosphorylated by Abl-1 to facilitate infection. Cell Microbiol 2007; 9:2644.
- Walker DH, Dumler JS. The role of CD8 T lymphocytes in rickettsial infections. Semin Immunopathol 2015; 37:289.
- Chen G, Severo MS, Sakhon OS, et al. Anaplasma phagocytophilum dihydrolipoamide dehydrogenase 1 affects host-derived immunopathology during microbial colonization. Infect Immun 2012; 80:3194.
- Choi KS, Webb T, Oelke M, et al. Differential innate immune cell activation and proinflammatory response in Anaplasma phagocytophilum infection. Infect Immun 2007; 75:3124.
- Zhang JZ, McBride JW, Yu XJ. L-selectin and E-selectin expressed on monocytes mediating Ehrlichia chaffeensis attachment onto host cells. FEMS Microbiol Lett 2003; 227:303.
- Mohan Kumar D, Yamaguchi M, Miura K, et al. Ehrlichia chaffeensis uses its surface protein EtpE to bind GPI-anchored protein DNase X and trigger entry into mammalian cells. PLoS Pathog 2013; 9:e1003666.
- Lin M, Rikihisa Y. Obligatory intracellular parasitism by Ehrlichia chaffeensis and Anaplasma phagocytophilum involves caveolae and glycosylphosphatidylinositol-anchored proteins. Cell Microbiol 2003; 5:809.
- Walker DH, Dumler JS. Human monocytic and granulocytic ehrlichioses. Discovery and diagnosis of emerging tick-borne infections and the critical role of the pathologist. Arch Pathol Lab Med 1997; 121:785.
- Sehdev AE, Dumler JS. Hepatic pathology in human monocytic ehrlichiosis. Ehrlichia chaffeensis infection. Am J Clin Pathol 2003; 119:859.
- Dunn BE, Monson TP, Dumler JS, et al. Identification of Ehrlichia chaffeensis morulae in cerebrospinal fluid mononuclear cells. J Clin Microbiol 1992; 30:2207.
- Dierberg KL, Dumler JS. Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME)? BMC Infect Dis 2006; 6:121.
- Dumler JS. Anaplasma and Ehrlichia infection. Ann N Y Acad Sci 2005; 1063:361.
- Ismail N, Walker DH, Ghose P, Tang YW. Immune mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis. BMC Immunol 2012; 13:26.
- Stevenson HL, Crossley EC, Thirumalapura N, et al. Regulatory roles of CD1d-restricted NKT cells in the induction of toxic shock-like syndrome in an animal model of fatal ehrlichiosis. Infect Immun 2008; 76:1434.
- Ismail N, Crossley EC, Stevenson HL, Walker DH. Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis. Infect Immun 2007; 75:4608.
- Luo T, Kuriakose JA, Zhu B, et al. Ehrlichia chaffeensis TRP120 interacts with a diverse array of eukaryotic proteins involved in transcription, signaling, and cytoskeleton organization. Infect Immun 2011; 79:4382.
- Granquist EG, Aleksandersen M, Bergström K, et al. A morphological and molecular study of Anaplasma phagocytophilum transmission events at the time of Ixodes ricinus tick bite. Acta Vet Scand 2010; 52:43.
- Dumler JS. The biological basis of severe outcomes in Anaplasma phagocytophilum infection. FEMS Immunol Med Microbiol 2012; 64:13.
- Lepidi H, Bunnell JE, Martin ME, et al. Comparative pathology, and immunohistology associated with clinical illness after Ehrlichia phagocytophila-group infections. Am J Trop Med Hyg 2000; 62:29.
- Dumler JS, Barat NC, Barat CE, Bakken JS. Human granulocytic anaplasmosis and macrophage activation. Clin Infect Dis 2007; 45:199.
- Yager E, Bitsaktsis C, Nandi B, et al. Essential role for humoral immunity during Ehrlichia infection in immunocompetent mice. Infect Immun 2005; 73:8009.
- Sun W, IJdo JW, Telford SR 3rd, et al. Immunization against the agent of human granulocytic ehrlichiosis in a murine model. J Clin Invest 1997; 100:3014.
- Birkner K, Steiner B, Rinkler C, et al. The elimination of Anaplasma phagocytophilum requires CD4+ T cells, but is independent of Th1 cytokines and a wide spectrum of effector mechanisms. Eur J Immunol 2008; 38:3395.
- Hess PR, English RV, Hegarty BC, et al. Experimental Ehrlichia canis infection in the dog does not cause immunosuppression. Vet Immunol Immunopathol 2006; 109:117.
- Magnarelli LA, Stafford KC 3rd, Ijdo JW, Fikrig E. Antibodies to whole-cell or recombinant antigens of Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti in white-footed mice. J Wildl Dis 2006; 42:732.
- Paddock CD, Yabsley MJ. Ecological havoc, the rise of white-tailed deer, and the emergence of Amblyomma americanum-associated zoonoses in the United States. Curr Top Microbiol Immunol 2007; 315:289.
- Kocan KM, de la Fuente J, Blouin EF, et al. The natural history of Anaplasma marginale. Vet Parasitol 2010; 167:95.
- TAXONOMY AND PHYLOGENY
- HOST SPECIFICITY
- CHARACTERISTICS OF ANAPLASMATACEAE
- General characteristics
- Growth characteristics
- Antigenic characteristics
- Cell specificity
- MECHANISMS OF DISEASE
- E. chaffeensis and human monocytic ehrlichiosis
- A. phagocytophilum and human granulocytic anaplasmosis
- IMMUNE RESPONSES