Antigenic diversity of granulocytic Ehrlichia isolates from humans in Wisconsin and New York and a horse in California.
Abstract: The agent of human granulocytic ehrlichiosis (HGE), Ehrlichia phagocytophila, and Ehrlichia equi are very similar. HGE is of variable severity. Genetic and antigenic differences among 3 human isolates (Webster, Spooner, and NY-8) and 1 horse isolate (MRK) were evaluated. The 16S rRNA gene sequences were identical in all human isolates. By use of 5 homologous antisera from these 3 humans and 1 horse and an additional 5 antisera in heterologous reactions, the immunodominant antigens of each isolate were noted to differ in molecular size: 43 kDa in the Webster (Wisconsin) isolate, 46 kDa in the Spooner (Wisconsin) isolate, 42 and 45 kDa in the NY-8 (New York State) isolate, and a 42 kDa doublet in the E. equi MRK isolate from California. Two sera from a Wisconsin patient reacted weakly or not at all with the NY-8 isolate. Antigenic structural diversity exists among otherwise indistinguishable granulocytic ehrlichial isolates.
Publication Date: 1997-10-23 PubMed ID: 9333162DOI: 10.1086/516529Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research article investigates the genetic and antigenic diversity among certain Ehrlichia isolates from three humans in Wisconsin and New York and a horse in California. The study finds that despite being genetically identical, these isolates present antigenic structural differences, leading to variability in human and animal disease severity.
Isolation of the Ehrlichia Strains
- The study features the comparison of different Ehrlichia strains that cause human granulocytic ehrlichiosis (HGE), a variable-severity disease transmitted by ticks, and a similar disease in horses (Ehrlichia equi).
- These strains are isolated from human patients from Wisconsin (Webster and Spooner strains) and New York State (NY-8 strain), and a horse from California (MRK strain).
Genetic Characterization
- The researchers conducted genetic sequencing of the 16S rRNA genes from each of these isolates. This gene is often used to identify and classify bacteria as it is both universally present and well-conserved across different bacterial species.
- All the human isolates showed identical sequences in this gene, suggesting a strong genetic similarity among them.
Antigenic Diversity
- Despite their genetic similarity, each isolate demonstrated unique antigenic properties. Antigens are proteins expressed by pathogens which the immune system recognizes and provokes an immune response against.
- Using antisera from these three humans and the horse, plus an additional five antisera, the study reveals differences in the molecular size of the dominant antigens among these isolates: 43 kDa from the Webster (Wisconsin) isolate, 46 kDa from the Spooner (Wisconsin) isolate, 42 and 45 kDa from the NY-8 (New York State) isolate, and a 42 kDa doublet from the E. equi MRK isolate from California.
- The distinct molecular sizes of the antigens signal different structures and functionalities of these proteins, leading to diversity in immunological response and hence, variability in disease severity.
Immune Response
- Further testing showed that two types of sera from a Wisconsin patient either weakly interacted with or failed to recognize the NY-8 isolate’s antigen. This suggested that the distinct antigenic structures of Ehrlichia strains could limit the effectiveness of certain immune responses towards different strains.
- This antigenic variation among Ehrlichia strains underscores the complex nature of host-pathogen interactions and the challenges in designing broad-effective therapeutic strategies or vaccines for HGE.
Cite This Article
APA
Asanovich KM, Bakken JS, Madigan JE, Aguero-Rosenfeld M, Wormser GP, Dumler JS.
(1997).
Antigenic diversity of granulocytic Ehrlichia isolates from humans in Wisconsin and New York and a horse in California.
J Infect Dis, 176(4), 1029-1034.
https://doi.org/10.1086/516529 Publication
Researcher Affiliations
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
MeSH Terms
- Animals
- Antibodies, Bacterial / analysis
- Antigens, Bacterial / analysis
- Cross Reactions / immunology
- DNA, Bacterial / analysis
- Ehrlichia / genetics
- Ehrlichia / immunology
- Ehrlichia / isolation & purification
- Ehrlichiosis / blood
- Ehrlichiosis / genetics
- Ehrlichiosis / immunology
- Horses
- Humans
- Immunoblotting
- Immunodominant Epitopes / analysis
- Polymerase Chain Reaction
- RNA, Ribosomal, 16S / genetics
- Sequence Homology, Nucleic Acid
Grant Funding
- AI-41213 / NIAID NIH HHS
Citations
This article has been cited 61 times.- Artigas-Jerónimo S, González-García A, de la Fuente J, Blanda V, Shekarkar Azgomi M, Villar M, Mohammadnezhad L, Grippi F, Torina A, Sireci G. Low NETosis Induced in Anaplasma phagocytophilum-Infected Cells.. Vaccines (Basel) 2022 Oct 20;10(10).
- Urbanová V, Kalinová E, Kopáček P, Šíma R. Experimental Infection of Mice and Ticks with the Human Isolate of Anaplasma phagocytophilum NY-18.. Pathogens 2022 Jul 21;11(7).
- Koku R, Herndon DR, Avillan J, Morrison J, Futse JE, Palmer GH, Brayton KA, Noh SM. Both Coinfection and Superinfection Drive Complex Anaplasma marginale Strain Structure in a Natural Transmission Setting.. Infect Immun 2021 Oct 15;89(11):e0016621.
- Müller BJ, Westheider A, Birkner K, Seelig B, Kirschnek S, Bogdan C, von Loewenich FD. Anaplasma phagocytophilum Induces TLR- and MyD88-Dependent Signaling in In Vitro Generated Murine Neutrophils.. Front Cell Infect Microbiol 2021;11:627630.
- Mateos-Hernández L, Pipová N, Allain E, Henry C, Rouxel C, Lagrée AC, Haddad N, Boulouis HJ, Valdés JJ, Alberdi P, de la Fuente J, Cabezas-Cruz A, Šimo L. Enlisting the Ixodes scapularis Embryonic ISE6 Cell Line to Investigate the Neuronal Basis of Tick-Pathogen Interactions.. Pathogens 2021 Jan 14;10(1).
- Estrada-Peña A, Villar M, Artigas-Jerónimo S, López V, Alberdi P, Cabezas-Cruz A, de la Fuente J. Use of Graph Theory to Characterize Human and Arthropod Vector Cell Protein Response to Infection With Anaplasma phagocytophilum.. Front Cell Infect Microbiol 2018;8:265.
- Diaz-Sanchez S, Hernández-Jarguín A, Fernández de Mera IG, Alberdi P, Zweygarth E, Gortazar C, de la Fuente J. Draft Genome Sequences of Anaplasma phagocytophilum, A. marginale, and A. ovis Isolates from Different Hosts.. Genome Announc 2018 Feb 1;6(5).
- Contreras M, Alberdi P, Fernández De Mera IG, Krull C, Nijhof A, Villar M, De La Fuente J. Vaccinomics Approach to the Identification of Candidate Protective Antigens for the Control of Tick Vector Infestations and Anaplasma phagocytophilum Infection.. Front Cell Infect Microbiol 2017;7:360.
- Contreras M, Alberdi P, Mateos-Hernández L, Fernández de Mera IG, García-Pérez AL, Vancová M, Villar M, Ayllón N, Cabezas-Cruz A, Valdés JJ, Stuen S, Gortazar C, de la Fuente J. Anaplasma phagocytophilum MSP4 and HSP70 Proteins Are Involved in Interactions with Host Cells during Pathogen Infection.. Front Cell Infect Microbiol 2017;7:307.
- Gussmann K, Kirschnek S, von Loewenich FD. Interferon-γ-dependent control of Anaplasma phagocytophilum by murine neutrophil granulocytes.. Parasit Vectors 2017 Jul 12;10(1):329.
- Cabezas-Cruz A, Alberdi P, Valdés JJ, Villar M, de la Fuente J. Anaplasma phagocytophilum Infection Subverts Carbohydrate Metabolic Pathways in the Tick Vector, Ixodes scapularis.. Front Cell Infect Microbiol 2017;7:23.
- Mansfield KL, Cook C, Ellis RJ, Bell-Sakyi L, Johnson N, Alberdi P, de la Fuente J, Fooks AR. Tick-borne pathogens induce differential expression of genes promoting cell survival and host resistance in Ixodes ricinus cells.. Parasit Vectors 2017 Feb 15;10(1):81.
- Al-Khedery B, Barbet AF. Comparative Genomics Identifies a Potential Marker of Human-Virulent Anaplasma phagocytophilum.. Pathogens 2014 Jan 9;3(1):25-35.
- Wang Y, Chen C, Zhang L. Molecular characterization of Msp2/P44 of Anaplasma phagocytophilum isolated from infected patients and Haemaphysalis longicornis in Laizhou Bay, Shandong Province, China.. PLoS One 2013;8(10):e78189.
- Galindo RC, Ayllón N, Smrdel KS, Boadella M, Beltrán-Beck B, Mazariegos M, García N, de la Lastra JM, Avsic-Zupanc T, Kocan KM, Gortazar C, de la Fuente J. Gene expression profile suggests that pigs (Sus scrofa) are susceptible to Anaplasma phagocytophilum but control infection.. Parasit Vectors 2012 Aug 30;5:181.
- Sarkar A, Hellberg L, Bhattacharyya A, Behnen M, Wang K, Lord JM, Möller S, Kohler M, Solbach W, Laskay T. Infection with Anaplasma phagocytophilum activates the phosphatidylinositol 3-Kinase/Akt and NF-κB survival pathways in neutrophil granulocytes.. Infect Immun 2012 Apr;80(4):1615-23.
- Rikihisa Y. Mechanisms of obligatory intracellular infection with Anaplasma phagocytophilum.. Clin Microbiol Rev 2011 Jul;24(3):469-89.
- Liesenfeld O, Parvanova I, Zerrahn J, Han SJ, Heinrich F, Muñoz M, Kaiser F, Aebischer T, Buch T, Waisman A, Reichmann G, Utermöhlen O, von Stebut E, von Loewenich FD, Bogdan C, Specht S, Saeftel M, Hoerauf A, Mota MM, Könen-Waisman S, Kaufmann SH, Howard JC. The IFN-γ-inducible GTPase, Irga6, protects mice against Toxoplasma gondii but not against Plasmodium berghei and some other intracellular pathogens.. PLoS One 2011;6(6):e20568.
- Zivkovic Z, Torina A, Mitra R, Alongi A, Scimeca S, Kocan KM, Galindo RC, Almazán C, Blouin EF, Villar M, Nijhof AM, Mani R, La Barbera G, Caracappa S, Jongejan F, de la Fuente J. Subolesin expression in response to pathogen infection in ticks.. BMC Immunol 2010 Feb 19;11:7.
- Bussmeyer U, Sarkar A, Broszat K, Lüdemann T, Möller S, van Zandbergen G, Bogdan C, Behnen M, Dumler JS, von Loewenich FD, Solbach W, Laskay T. Impairment of gamma interferon signaling in human neutrophils infected with Anaplasma phagocytophilum.. Infect Immun 2010 Jan;78(1):358-63.
- Scorpio DG, Leutenegger C, Berger J, Barat N, Madigan JE, Dumler JS. Sequential analysis of Anaplasma phagocytophilum msp2 transcription in murine and equine models of human granulocytic anaplasmosis.. Clin Vaccine Immunol 2008 Mar;15(3):418-24.
- Shukla SK, Aswani V, Stockwell PJ, Reed KD. Contribution of polymorphisms in ankA, gltA, and groESL in defining genetic variants of Anaplasma phagocytophilum.. J Clin Microbiol 2007 Jul;45(7):2312-5.
- de la Fuente J, Almazán C, Blouin EF, Naranjo V, Kocan KM. Reduction of tick infections with Anaplasma marginale and A. phagocytophilum by targeting the tick protective antigen subolesin.. Parasitol Res 2006 Dec;100(1):85-91.
- Teglas MB, Foley J. Differences in the transmissibility of two Anaplasma phagocytophilum strains by the North American tick vector species, Ixodes pacificus and Ixodes scapularis (Acari: Ixodidae).. Exp Appl Acarol 2006;38(1):47-58.
- Dreher UM, de la Fuente J, Hofmann-Lehmann R, Meli ML, Pusterla N, Kocan KM, Woldehiwet Z, Braun U, Regula G, Staerk KD, Lutz H. Serologic cross-reactivity between Anaplasma marginale and Anaplasma phagocytophilum.. Clin Diagn Lab Immunol 2005 Oct;12(10):1177-83.
- de la Fuente J, Massung RF, Wong SJ, Chu FK, Lutz H, Meli M, von Loewenich FD, Grzeszczuk A, Torina A, Caracappa S, Mangold AJ, Naranjo V, Stuen S, Kocan KM. Sequence analysis of the msp4 gene of Anaplasma phagocytophilum strains.. J Clin Microbiol 2005 Mar;43(3):1309-17.
- Poitout FM, Shinozaki JK, Stockwell PJ, Holland CJ, Shukla SK. Genetic variants of Anaplasma phagocytophilum infecting dogs in Western Washington State.. J Clin Microbiol 2005 Feb;43(2):796-801.
- Levin ML, Coble DJ, Ross DE. Reinfection with Anaplasma phagocytophilum in BALB/c mice and cross-protection between two sympatric isolates.. Infect Immun 2004 Aug;72(8):4723-30.
- Lin Q, Rikihisa Y, Felek S, Wang X, Massung RF, Woldehiwet Z. Anaplasma phagocytophilum has a functional msp2 gene that is distinct from p44.. Infect Immun 2004 Jul;72(7):3883-9.
- Felek S, Telford S 3rd, Falco RC, Rikihisa Y. Sequence analysis of p44 homologs expressed by Anaplasma phagocytophilum in infected ticks feeding on naive hosts and in mice infected by tick attachment.. Infect Immun 2004 Feb;72(2):659-66.
- Scorpio DG, Caspersen K, Ogata H, Park J, Dumler JS. Restricted changes in major surface protein-2 (msp2) transcription after prolonged in vitro passage of Anaplasma phagocytophilum.. BMC Microbiol 2004 Jan 8;4:1.
- Park JH, Heo EJ, Choi KS, Dumler JS, Chae JS. Detection of antibodies to Anaplasma phagocytophilum and Ehrlichia chaffeensis antigens in sera of Korean patients by western immunoblotting and indirect immunofluorescence assays.. Clin Diagn Lab Immunol 2003 Nov;10(6):1059-64.
- Dumler JS, Asanovich KM, Bakken JS. Analysis of genetic identity of North American Anaplasma phagocytophilum strains by pulsed-field gel electrophoresis.. J Clin Microbiol 2003 Jul;41(7):3392-4.
- Park J, Choi KS, Dumler JS. Major surface protein 2 of Anaplasma phagocytophilum facilitates adherence to granulocytes.. Infect Immun 2003 Jul;71(7):4018-25.
- Barbet AF, Meeus PF, Bélanger M, Bowie MV, Yi J, Lundgren AM, Alleman AR, Wong SJ, Chu FK, Munderloh UG, Jauron SD. Expression of multiple outer membrane protein sequence variants from a single genomic locus of Anaplasma phagocytophilum.. Infect Immun 2003 Apr;71(4):1706-18.
- Maurin M, Bakken JS, Dumler JS. Antibiotic susceptibilities of Anaplasma (Ehrlichia) phagocytophilum strains from various geographic areas in the United States.. Antimicrob Agents Chemother 2003 Jan;47(1):413-5.
- Heo EJ, Park JH, Koo JR, Park MS, Park MY, Dumler JS, Chae JS. Serologic and molecular detection of Ehrlichia chaffeensis and Anaplasma phagocytophila (human granulocytic ehrlichiosis agent) in Korean patients.. J Clin Microbiol 2002 Aug;40(8):3082-5.
- Aguero-Rosenfeld ME, Donnarumma L, Zentmaier L, Jacob J, Frey M, Noto R, Carbonaro CA, Wormser GP. Seroprevalence of antibodies that react with Anaplasma phagocytophila, the agent of human granulocytic ehrlichiosis, in different populations in Westchester County, New York.. J Clin Microbiol 2002 Jul;40(7):2612-5.
- Smith AL, Hesketh P, Archer A, Shirley MW. Antigenic diversity in Eimeria maxima and the influence of host genetics and immunization schedule on cross-protective immunity.. Infect Immun 2002 May;70(5):2472-9.
- Stuen S, Bergström K. Serological investigation of granulocytic Ehrlichia infection in sheep in Norway.. Acta Vet Scand 2001;42(3):331-8.
- Bjöersdorff A, Bagert B, Massung RF, Gusa A, Eliasson I. Isolation and characterization of two European strains of Ehrlichia phagocytophila of equine origin.. Clin Diagn Lab Immunol 2002 Mar;9(2):341-3.
- Caspersen K, Park JH, Patil S, Dumler JS. Genetic variability and stability of Anaplasma phagocytophila msp2 (p44).. Infect Immun 2002 Mar;70(3):1230-4.
- Zhi N, Ohashi N, Tajima T, Mott J, Stich RW, Grover D, Telford SR 3rd, Lin Q, Rikihisa Y. Transcript heterogeneity of the p44 multigene family in a human granulocytic ehrlichiosis agent transmitted by ticks.. Infect Immun 2002 Mar;70(3):1175-84.
- Carter SE, Ravyn MD, Xu Y, Johnson RC. Molecular typing of the etiologic agent of human granulocytic ehrlichiosis.. J Clin Microbiol 2001 Sep;39(9):3398-401.
- Martin ME, Caspersen K, Dumler JS. Immunopathology and ehrlichial propagation are regulated by interferon-gamma and interleukin-10 in a murine model of human granulocytic ehrlichiosis.. Am J Pathol 2001 May;158(5):1881-8.
- Brouqui P, Salvo E, Dumler JS, Raoult D. Diagnosis of granulocytic ehrlichiosis in humans by immunofluorescence assay.. Clin Diagn Lab Immunol 2001 Jan;8(1):199-202.
- Ravyn MD, Kodner CB, Carter SE, Jarnefeld JL, Johnson RC. Isolation of the etiologic agent of human granulocytic ehrlichiosis from the white-footed mouse (Peromyscus leucopus).. J Clin Microbiol 2001 Jan;39(1):335-8.
- Caturegli P, Asanovich KM, Walls JJ, Bakken JS, Madigan JE, Popov VL, Dumler JS. ankA: an Ehrlichia phagocytophila group gene encoding a cytoplasmic protein antigen with ankyrin repeats.. Infect Immun 2000 Sep;68(9):5277-83.
- Chae JS, Foley JE, Dumler JS, Madigan JE. Comparison of the nucleotide sequences of 16S rRNA, 444 Ep-ank, and groESL heat shock operon genes in naturally occurring Ehrlichia equi and human granulocytic ehrlichiosis agent isolates from Northern California.. J Clin Microbiol 2000 Apr;38(4):1364-9.
- Pusterla N, Madigan JE, Asanovich KM, Chae JS, Derock E, Leutenegger CM, Pusterla JB, Lutz H, Dumler JS. Experimental inoculation with human granulocytic Ehrlichia agent derived from high- and low-passage cell culture in horses.. J Clin Microbiol 2000 Mar;38(3):1276-8.
- Aguero-Rosenfeld ME, Kalantarpour F, Baluch M, Horowitz HW, McKenna DF, Raffalli JT, Hsieh Tc, Wu J, Dumler JS, Wormser GP. Serology of culture-confirmed cases of human granulocytic ehrlichiosis.. J Clin Microbiol 2000 Feb;38(2):635-8.
- Chang YF, McDonough SP, Chang CF, Shin KS, Yen W, Divers T. Human granulocytic ehrlichiosis agent infection in a pony vaccinated with a Borrelia burgdorferi recombinant OspA vaccine and challenged by exposure to naturally infected ticks.. Clin Diagn Lab Immunol 2000 Jan;7(1):68-71.
- IJdo JW, Wu C, Magnarelli LA, Fikrig E. Serodiagnosis of human granulocytic ehrlichiosis by a recombinant HGE-44-based enzyme-linked immunosorbent assay.. J Clin Microbiol 1999 Nov;37(11):3540-4.
- Walls JJ, Aguero-Rosenfeld M, Bakken JS, Goodman JL, Hossain D, Johnson RC, Dumler JS. Inter- and intralaboratory comparison of Ehrlichia equi and human granulocytic ehrlichiosis (HGE) agent strains for serodiagnosis of HGE by the immunofluorescent-antibody test.. J Clin Microbiol 1999 Sep;37(9):2968-73.
- Stafford KC 3rd, Massung RF, Magnarelli LA, Ijdo JW, Anderson JF. Infection with agents of human granulocytic ehrlichiosis, lyme disease, and babesiosis in wild white-footed mice (Peromyscus leucopus) in Connecticut.. J Clin Microbiol 1999 Sep;37(9):2887-92.
- Walls JJ, Asanovich KM, Bakken JS, Dumler JS. Serologic evidence of a natural infection of white-tailed deer with the agent of human granulocytic ehrlichiosis in Wisconsin and Maryland.. Clin Diagn Lab Immunol 1998 Nov;5(6):762-5.
- Magnarelli LA, Ijdo JW, Anderson JF, Padula SJ, Flavell RA, Fikrig E. Human exposure to a granulocytic Ehrlichia and other tick-borne agents in Connecticut.. J Clin Microbiol 1998 Oct;36(10):2823-7.
- Murphy CI, Storey JR, Recchia J, Doros-Richert LA, Gingrich-Baker C, Munroe K, Bakken JS, Coughlin RT, Beltz GA. Major antigenic proteins of the agent of human granulocytic ehrlichiosis are encoded by members of a multigene family.. Infect Immun 1998 Aug;66(8):3711-8.
- Ijdo JW, Sun W, Zhang Y, Magnarelli LA, Fikrig E. Cloning of the gene encoding the 44-kilodalton antigen of the agent of human granulocytic ehrlichiosis and characterization of the humoral response.. Infect Immun 1998 Jul;66(7):3264-9.
- Zhi N, Ohashi N, Rikihisa Y, Horowitz HW, Wormser GP, Hechemy K. Cloning and expression of the 44-kilodalton major outer membrane protein gene of the human granulocytic ehrlichiosis agent and application of the recombinant protein to serodiagnosis.. J Clin Microbiol 1998 Jun;36(6):1666-73.
- Ravyn MD, Goodman JL, Kodner CB, Westad DK, Coleman LA, Engstrom SM, Nelson CM, Johnson RC. Immunodiagnosis of human granulocytic ehrlichiosis by using culture-derived human isolates.. J Clin Microbiol 1998 Jun;36(6):1480-8.
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