Evans Sean M, Adcox Haley E, VieBrock Lauren, Green Ryan S, Luce-Fedrow Alison, Chattopadhyay Suschsmita, Jiang Ju, Marconi Richard T, Paris Daniel, Richards Allen L, Carlyon Jason A
Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, School of Medicine, Richmond, VA 23298, USA.
Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD 20910, USA.
Trop Med Infect Dis. 2018 Jun 11;3(2):63. doi: 10.3390/tropicalmed3020063.
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 . 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 isolates. Molecular modeling revealed the predicted tertiary structure of OmpA to be very similar to that of the phylogenetically-related pathogen, , including the location of a helix that contains residues functionally essential for infection. PCR primers were developed that amplified DNA from all strains, but not from negative control bacteria. Using these primers in quantitative PCR enabled sensitive detection and quantitation of 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 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.
恙虫病立克次体病威胁着亚太地区的10亿人口,且在该地区以外也出现了病例。它是由感染该细菌的众多菌株中的任何一种引起的。目前缺乏一种能提供异源保护的疫苗和一种可商购的分子诊断检测方法。在此,我们确定外膜蛋白A(OmpA)的核苷酸和翻译后的氨基酸序列在51株分离株中高度保守。分子建模显示,预测的OmpA三级结构与系统发育相关病原体的结构非常相似,包括一个含有对感染至关重要的功能残基的螺旋结构的位置。开发了能从所有菌株中扩增DNA,但不能从阴性对照细菌中扩增DNA的PCR引物。使用这些引物进行定量PCR能够灵敏地检测和定量来自经实验感染Karp或Gilliam菌株的小鼠器官和血液中的DNA。菌株间OmpA的高度保守证明了其作为分子诊断靶点的潜力,并证明将其作为开发一种具有广泛保护作用的恙虫病立克次体病疫苗的候选物是合理的。