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PMID: 16482227 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Comparative genomics of emerging human ehrlichiosis agents.

PLoS genetics ·Vol. 2 ·No. 2 ·2006-02-00 ·Pages e21

Dunning Hotopp JC, Lin M, Madupu R, Crabtree J, Angiuoli SV, Eisen JA, Eisen J, Seshadri R, Ren Q, Wu M, Utterback TR, Smith S, Lewis M, Khouri H, Zhang C, Niu H, Lin Q, Ohashi N, Zhi N, Nelson W, Brinkac LM, Dodson RJ, Rosovitz MJ, Sundaram J, Daugherty SC, Davidsen T, Durkin AS, Gwinn M, Haft DH, Selengut JD, Sullivan SA, Zafar N, Zhou L, Benahmed F, Forberger H, Halpin R, Mulligan S, Robinson J, White O, Rikihisa Y, Tettelin H

Abstract

Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.

MeSH Terms
Animals Biotin/metabolism DNA Repair Ehrlichia/genetics Ehrlichiosis/genetics,microbiology Genome Genomics/methods Humans Models, Biological Phylogeny Rickettsia/genetics Ticks
Chemicals
Biotin
Authors & Affiliations
41 authors, click to expand affiliations / ORCID
Dunning Hotopp Julie C
The Institute for Genomic Research, Rockville, Maryland, USA. [email protected]
Lin Mingqun
Madupu Ramana
Crabtree Jonathan
Angiuoli Samuel V
Eisen Jonathan A
Eisen Jonathan
Seshadri Rekha
Ren Qinghu
Wu Martin
Utterback Teresa R
Smith Shannon
Lewis Matthew
Khouri Hoda
Zhang Chunbin
Niu Hua
Lin Quan
Ohashi Norio
Zhi Ning
Nelson William
Brinkac Lauren M
Dodson Robert J
Rosovitz M J
Sundaram Jaideep
Daugherty Sean C
Davidsen Tanja
Durkin Anthony S
Gwinn Michelle
Haft Daniel H
Selengut Jeremy D
Sullivan Steven A
Zafar Nikhat
Zhou Liwei
Benahmed Faiza
Forberger Heather
Halpin Rebecca
Mulligan Stephanie
Robinson Jeffrey
White Owen
Rikihisa Yasuko
Tettelin Hervé
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

References (81)
81 references, click to expand
  1. The genome sequence of Blochmannia floridanus: comparative analysis of reduced genomes.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9388-93 PMID: 12886019
  2. Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival.
    Infect Immun. 2003 Sep;71(9):5324-31 PMID: 12933880
  3. Mechanisms of variable p44 expression by Anaplasma phagocytophilum.
    Infect Immun. 2003 Oct;71(10):5650-61 PMID: 14500485
  4. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood.
    Syst Biol. 2003 Oct;52(5):696-704 PMID: 14530136
  5. The Pfam protein families database.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41 PMID: 14681378
  6. TransportDB: a relational database of cellular membrane transport systems.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D284-8 PMID: 14681414
  7. MetaCyc: a multiorganism database of metabolic pathways and enzymes.
    Nucleic Acids Res. 2004 Jan 1;32(Database issue):D438-42 PMID: 14681452
  8. 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 PMID: 14742506
  9. Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements.
    PLoS Biol. 2004 Mar;2(3):E69 PMID: 15024419
  10. Characterization of a major outer membrane protein multigene family in Ehrlichia ruminantium.
    Gene. 2004 Apr 14;330:159-68 PMID: 15087135
  11. Tryptophan recycling is responsible for the interferon-gamma resistance of Chlamydia psittaci GPIC in indoleamine dioxygenase-expressing host cells.
    Mol Microbiol. 2004 May;52(3):903-16 PMID: 15101993
  12. The genome sequence of Rickettsia prowazekii and the origin of mitochondria.
    Nature. 1998 Nov 12;396(6707):133-40 PMID: 9823893
  13. Molecular cloning and characterization of the Ehrlichia chaffeensis variable-length PCR target: an antigen-expressing gene that exhibits interstrain variation.
    J Clin Microbiol. 1999 May;37(5):1447-53 PMID: 10203503
  14. Multiple p44 genes encoding major outer membrane proteins are expressed in the human granulocytic ehrlichiosis agent.
    J Biol Chem. 1999 Jun 18;274(25):17828-36 PMID: 10364227
  15. REPuter: fast computation of maximal repeats in complete genomes.
    Bioinformatics. 1999 May;15(5):426-7 PMID: 10366664
  16. Rapid sequential changeover of expressed p44 genes during the acute phase of Anaplasma phagocytophilum infection in horses.
    Infect Immun. 2004 Dec;72(12):6852-9 PMID: 15557606
  17. Metabolic interdependence of obligate intracellular bacteria and their insect hosts.
    Microbiol Mol Biol Rev. 2004 Dec;68(4):745-70 PMID: 15590782
  18. 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 Jan 18;102(3):844-9 PMID: 15618402
  19. Effect of antibody on the rickettsia-host cell interaction.
    Infect Immun. 2004 Jun;72(6):3524-30 PMID: 15155660
  20. The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae.
    Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9716-21 PMID: 15210978
  21. Anaplasma phagocytophilum utilizes multiple host evasion mechanisms to thwart NADPH oxidase-mediated killing during neutrophil infection.
    Infect Immun. 2004 Aug;72(8):4772-83 PMID: 15271939
  22. Analysis of p51, groESL, and the major antigen P51 in various species of Neorickettsia, an obligatory intracellular bacterium that infects trematodes and mammals.
    J Clin Microbiol. 2004 Aug;42(8):3823-6 PMID: 15297539
  23. Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae.
    J Bacteriol. 2004 Sep;186(17):5842-55 PMID: 15317790
  24. Enhanced functional and structural domain assignments using remote similarity detection procedures for proteins encoded in the genome of Mycobacterium tuberculosis H37Rv.
    J Biosci. 2004 Sep;29(3):245-59 PMID: 15381846
  25. Polymorphism and transcription at the p44-1/p44-18 genomic locus in Anaplasma phagocytophilum strains from diverse geographic regions.
    Infect Immun. 2004 Oct;72(10):5574-81 PMID: 15385454
  26. Human infection with Ehrlichia canis, a leukocytic rickettsia.
    N Engl J Med. 1987 Apr 2;316(14):853-6 PMID: 3029590
  27. [Two cases of spotted fever rickettsiosis in Kyushu].
    Kansenshogaku Zasshi. 1987 Oct;61(10):1166-72 PMID: 3130435
  28. The tribe Ehrlichieae and ehrlichial diseases.
    Clin Microbiol Rev. 1991 Jul;4(3):286-308 PMID: 1889044
  29. Isolation and characterization of an Ehrlichia sp. from a patient diagnosed with human ehrlichiosis.
    J Clin Microbiol. 1991 Dec;29(12):2741-5 PMID: 1757543
  30. Ehrlichia chaffeensis, a new species associated with human ehrlichiosis.
    J Clin Microbiol. 1991 Dec;29(12):2838-42 PMID: 1757557
  31. L-arginine-dependent killing of intracellular Ehrlichia risticii by macrophages treated with gamma interferon.
    Infect Immun. 1992 Sep;60(9):3504-8 PMID: 1323533
  32. Cytochrome oxidase evolved by tinkering with denitrification enzymes.
    FEBS Lett. 1994 Mar 14;341(1):1-4 PMID: 8137905
  33. The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode.
    PLoS Biol. 2005 Apr;3(4):e121 PMID: 15780005
  34. Establishment of cloned Anaplasma phagocytophilum and analysis of p44 gene conversion within an infected horse and infected SCID mice.
    Infect Immun. 2005 Aug;73(8):5106-14 PMID: 16041027
  35. Human granulocytic anaplasmosis and Anaplasma phagocytophilum.
    Emerg Infect Dis. 2005 Dec;11(12):1828-34 PMID: 16485466
  36. Improved microbial gene identification with GLIMMER.
    Nucleic Acids Res. 1999 Dec 1;27(23):4636-41 PMID: 10556321
  37. Molecular cloning and characterization of the 120-kilodalton protein gene of Ehrlichia canis and application of the recombinant 120-kilodalton protein for serodiagnosis of canine ehrlichiosis.
    J Clin Microbiol. 2000 Jan;38(1):369-74 PMID: 10618118
  38. Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39.
    Nucleic Acids Res. 2000 Mar 15;28(6):1397-406 PMID: 10684935
  39. A whole-genome assembly of Drosophila.
    Science. 2000 Mar 24;287(5461):2196-204 PMID: 10731133
  40. Characterization of the complete transcriptionally active ehrlichia chaffeensis 28 kDa outer membrane protein multigene family.
    Gene. 2000 May 2;248(1-2):59-68 PMID: 10806351
  41. New functions for the ancient globin family: bacterial responses to nitric oxide and nitrosative stress.
    Mol Microbiol. 2000 May;36(4):775-83 PMID: 10844666
  42. Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp. APS.
    Nature. 2000 Sep 7;407(6800):81-6 PMID: 10993077
  43. Evidence for symmetric chromosomal inversions around the replication origin in bacteria.
    Genome Biol. 2000;1(6):RESEARCH0011 PMID: 11178265
  44. Analysis of transcriptionally active gene clusters of major outer membrane protein multigene family in Ehrlichia canis and E. chaffeensis.
    Infect Immun. 2001 Apr;69(4):2083-91 PMID: 11254561
  45. Complete genome sequence of Caulobacter crescentus.
    Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4136-41 PMID: 11259647
  46. Complete genome sequence of a virulent isolate of Streptococcus pneumoniae.
    Science. 2001 Jul 20;293(5529):498-506 PMID: 11463916
  47. A clustering method for repeat analysis in DNA sequences.
    Genome Biol. 2001;2(8):RESEARCH0027 PMID: 11532211
  48. Mechanisms of evolution in Rickettsia conorii and R. prowazekii.
    Science. 2001 Sep 14;293(5537):2093-8 PMID: 11557893
  49. Cloning, expression, purification and characterization of patatin, a novel phospholipase A.
    Eur J Biochem. 2001 Oct;268(19):5037-44 PMID: 11589694
  50. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease.
    J Clin Microbiol. 1994 Mar;32(3):589-95 PMID: 8195363
  51. Intermolecular relationships of major surface proteins of Anaplasma marginale.
    Infect Immun. 1994 Jul;62(7):2940-6 PMID: 8005681
  52. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd.
    Science. 1995 Jul 28;269(5223):496-512 PMID: 7542800
  53. Direct cultivation of the causative agent of human granulocytic ehrlichiosis.
    N Engl J Med. 1996 Jan 25;334(4):209-15 PMID: 8531996
  54. Asymmetric substitution patterns in the two DNA strands of bacteria.
    Mol Biol Evol. 1996 May;13(5):660-5 PMID: 8676740
  55. Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle.
    Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):6209-14 PMID: 8650245
  56. Microbial gene identification using interpolated Markov models.
    Nucleic Acids Res. 1998 Jan 15;26(2):544-8 PMID: 9421513
  57. Immunodominant major outer membrane proteins of Ehrlichia chaffeensis are encoded by a polymorphic multigene family.
    Infect Immun. 1998 Jan;66(1):132-9 PMID: 9423849
  58. Human ehrlichioses: newly recognized infections transmitted by ticks.
    Annu Rev Med. 1998;49:201-13 PMID: 9509259
  59. Reductive evolution of resident genomes.
    Trends Microbiol. 1998 Jul;6(7):263-8 PMID: 9717214
  60. The genome of the heartwater agent Ehrlichia ruminantium contains multiple tandem repeats of actively variable copy number.
    Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):838-43 PMID: 15637156
  61. Positive charge is an important feature of the C-terminal transport signal of the VirB/D4-translocated proteins of Agrobacterium.
    Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):832-7 PMID: 15644442
  62. Neorickettsia risticii is vertically transmitted in the trematode Acanthatrium oregonense and horizontally transmitted to bats.
    Environ Microbiol. 2005 Feb;7(2):203-12 PMID: 15658987
  63. Genome Properties: a system for the investigation of prokaryotic genetic content for microbiology, genome annotation and comparative genomics.
    Bioinformatics. 2005 Feb 1;21(3):293-306 PMID: 15347579
  64. Involvement of the twin-arginine translocation system in protein secretion via the type II pathway.
    EMBO J. 2001 Dec 3;20(23):6735-41 PMID: 11726509
  65. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila.
    Int J Syst Evol Microbiol. 2001 Nov;51(Pt 6):2145-65 PMID: 11760958
  66. Chromosome loss from par mutants of Pseudomonas putida depends on growth medium and phase of growth.
    Microbiology. 2002 Feb;148(Pt 2):537-48 PMID: 11832517
  67. Transcript heterogeneity of the p44 multigene family in a human granulocytic ehrlichiosis agent transmitted by ticks.
    Infect Immun. 2002 Mar;70(3):1175-84 PMID: 11854198
  68. Characterization and transcriptional analysis of gene clusters for a type IV secretion machinery in human granulocytic and monocytic ehrlichiosis agents.
    Infect Immun. 2002 Apr;70(4):2128-38 PMID: 11895979
  69. The omp-1 major outer membrane multigene family of Ehrlichia chaffeensis is differentially expressed in canine and tick hosts.
    Infect Immun. 2002 Aug;70(8):4701-4 PMID: 12117987
  70. Analysis of sequences and loci of p44 homologs expressed by Anaplasma phagocytophila in acutely infected patients.
    J Clin Microbiol. 2002 Aug;40(8):2981-8 PMID: 12149362
  71. Bacterial chromosome segregation.
    Annu Rev Microbiol. 2002;56:567-97 PMID: 12142478
  72. The Brucella suis genome reveals fundamental similarities between animal and plant pathogens and symbionts.
    Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13148-53 PMID: 12271122
  73. Genome sequence of the endocellular obligate symbiont of tsetse flies, Wigglesworthia glossinidia.
    Nat Genet. 2002 Nov;32(3):402-7 PMID: 12219091
  74. Ehrlichia chaffeensis: a prototypical emerging pathogen.
    Clin Microbiol Rev. 2003 Jan;16(1):37-64 PMID: 12525424
  75. TM4: a free, open-source system for microarray data management and analysis.
    Biotechniques. 2003 Feb;34(2):374-8 PMID: 12613259
  76. Expression of multiple outer membrane protein sequence variants from a single genomic locus of Anaplasma phagocytophilum.
    Infect Immun. 2003 Apr;71(4):1706-18 PMID: 12654783
  77. Complete genome sequence of the Q-fever pathogen Coxiella burnetii.
    Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5455-60 PMID: 12704232
  78. Inducible nitric oxide synthase and control of intracellular bacterial pathogens.
    Microbes Infect. 2003 Jun;5(7):621-7 PMID: 12787738
  79. Escherichia coli flavohemoglobin is an efficient alkylhydroperoxide reductase.
    J Biol Chem. 2003 Jun 20;278(25):22272-7 PMID: 12663656
  80. Mechanisms to create a safe haven by members of the family Anaplasmataceae.
    Ann N Y Acad Sci. 2003 Jun;990:548-55 PMID: 12860688
  81. Tropheryma whipplei Twist: a human pathogenic Actinobacteria with a reduced genome.
    Genome Res. 2003 Aug;13(8):1800-9 PMID: 12902375
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
Published
2006-02-00
Epub
2006-00-17
Pages
e21
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1366493
Subset
IM
Grants
NIAID NIH HHS · R01 AI047885 · United States
NIAID NIH HHS · R01 AI47885 · United States
Corrections
ErratumIn
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