title: Diversity of the 47-kD HtrA nucleic acid and translated amino acid sequences from 17 recent human isolates of Orientia.
abstract: Orientia tsutsugamushi, the etiologic agent of potentially fatal scrub typhus, is characterized by a high antigenic diversity, which complicates the development of a broadly protective vaccine. Efficacy studies in murine and nonhuman primate models demonstrated the DNA vaccine candidate pKarp47, based upon the O. tsutsugamushi Karp 47-kD HtrA protein gene, to be a successful immunoprophylactic against scrub typhus. To characterize 47-kD HtrA protein diversity among human isolates of Orientia, we sequenced the full open reading frame (ORF) of the 47-kD HtrA gene and analyzed the translated amino acid sequences of 17 patient isolates from Thailand (n=13), Laos (n=2), Australia (n=1), and the United Arab Emirates (UAE) (n=1) and 9 reference strains: Karp (New Guinea), Kato (Japan), Ikeda (Japan), Gilliam (Burma), Boryong (Korea), TA763, TH1811 and TH1817 (Thailand), and MAK243 (China). The percentage identity (similarity) of translated amino acid sequences between 16 new isolates and 9 reference strains of O. tsutsugamushi ranged from 96.4% to 100% (97.4% to 100%). However, inclusion of the recently identified Orientia chuto sp. nov. reduced identity (similarity) values to 82.2% to 83.3% (90.4% to 91.4%). These results demonstrate the diversity of Orientia 47-kD HtrA among isolates encountered by humans and therefore provide support for the necessity of developing a broadly protective scrub typhus vaccine that takes this diversity into account.
authors.affiliation: Naval Medical Research Center , Silver Spring, Maryland, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Jiang
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Paris
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Blacksell
authors.forename: Nuntipa
authors.initials: N
authors.lastname: Aukkanit
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Rattanaphone
authors.initials: R
authors.lastname: Phetsouvanh
authors.forename: Leonard
authors.initials: L
authors.lastname: Izzard
authors.forename: John
authors.initials: J
authors.lastname: Stenos
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Graves
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Allen L
authors.initials: AL
authors.lastname: Richards
mesh_terms: D000595:Amino Acid Sequence; D000940:Antigenic Variation / Q000235:genetics*; D001315:Australia / Q000453:epidemiology; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005838:Genotype; D006801:Humans; D007812:Laos / Q000453:epidemiology; D008969:Molecular Sequence Data; D012285:Orientia tsutsugamushi / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D010802:Phylogeny; D012612:Scrub Typhus / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D017422:Sequence Analysis, DNA; D013785:Thailand / Q000453:epidemiology; D014479:United Arab Emirates / Q000453:epidemiology
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers