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Trop. Med. Infect. Dis. 2018, 3(2), 63; https://doi.org/10.3390/tropicalmed3020063

Outer Membrane Protein A Conservation among Orientia tsutsugamushi Isolates Suggests Its Potential as a Protective Antigen and Diagnostic Target

1
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA
2
Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA
3
Department of Biology, Shippensburg University, Shippensburg, PA 17257, USA
4
Department of Medicine, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland
5
Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Present address: Virology and Serology Department, Infectious Diseases Laboratory, Utah Public Health Lab, Taylorsville, UT 84129, USA.
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 11 April 2018 / Revised: 31 May 2018 / Accepted: 4 June 2018 / Published: 11 June 2018
(This article belongs to the Special Issue The Past and Present Threat of Rickettsial Diseases)
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Abstract

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially-available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically-related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs and blood of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly-protective scrub typhus vaccine. View Full-Text
Keywords: scrub typhus; Orientia tsutsugamushi; Rickettsia; Rickettsiales; outer membrane protein A; Anaplasma scrub typhus; Orientia tsutsugamushi; Rickettsia; Rickettsiales; outer membrane protein A; Anaplasma
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    Description: Table S1. Nucleotide and amino acid identity values for O. tsutsugamushi OmpA sequences
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Evans, S.M.; Adcox, H.E.; VieBrock, L.; Green, R.S.; Luce-Fedrow, A.; Chattopadhyay, S.; Jiang, J.; Marconi, R.T.; Paris, D.; Richards, A.L.; Carlyon, J.A. Outer Membrane Protein A Conservation among Orientia tsutsugamushi Isolates Suggests Its Potential as a Protective Antigen and Diagnostic Target. Trop. Med. Infect. Dis. 2018, 3, 63.

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