PLoS ONE (Jan 2018)

Significance of a histone-like protein with its native structure for the diagnosis of asymptomatic tuberculosis.

  • Yukiko Ohara,
  • Yuriko Ozeki,
  • Yoshitaka Tateishi,
  • Tsukasa Mashima,
  • Fumio Arisaka,
  • Yasuo Tsunaka,
  • Yoshie Fujiwara,
  • Akihito Nishiyama,
  • Yutaka Yoshida,
  • Kengo Kitadokoro,
  • Haruka Kobayashi,
  • Yukihiro Kaneko,
  • Ichiro Nakagawa,
  • Ryoji Maekura,
  • Saburo Yamamoto,
  • Masato Katahira,
  • Sohkichi Matsumoto

DOI
https://doi.org/10.1371/journal.pone.0204160
Journal volume & issue
Vol. 13, no. 10
p. e0204160

Abstract

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Tuberculosis causes the highest mortality among all single infections. Asymptomatic tuberculosis, afflicting one third of the global human population, is the major source as 5-10% of asymptomatic cases develop active tuberculosis during their lifetime. Thus it is one of important issues to develop diagnostic tools for accurately detecting asymptomatic infection. Mycobacterial DNA-binding protein 1 (MDP1) is a major protein in persistent Mycobacterium tuberculosis and has potential for diagnostic use in detecting asymptomatic infection. However, a previous ELISA-based study revealed a specificity problem; IgGs against MDP1 were detected in both M. tuberculosis-infected and uninfected individuals. Although the tertiary structures of an antigen are known to influence antibody recognition, the MDP1 structural details have not yet been investigated. The N-terminal half of MDP1, homologous to bacterial histone-like protein HU, is predicted to be responsible for DNA-binding, while the C-terminal half is assumed as totally intrinsically disordered regions. To clarify the relationship between the MDP1 tertiary structure and IgG recognition, we refined the purification method, which allow us to obtain a recombinant protein with the predicted structure. Furthermore, we showed that an IgG-ELISA using MDP1 purified by our refined method is indeed useful in the detection of asymptomatic tuberculosis.