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PLoS One. 2018 Oct 25;13(10):e0204160. doi: 10.1371/journal.pone.0204160. eCollection 2018.

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

Author information

1
Department of Bacteriology, Niigata University School of Medicine, Niigata, Japan.
2
Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan.
3
Graduate School of Energy Science, Kyoto University, Gokasho, Uji, Kyoto, Japan.
4
College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan.
5
Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Japan.
6
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto, Japan.
7
Department of Structural Pathology, Institute of Nephrology, Graduate School of Medicine, Niigata University, Niigata, Japan.
8
Graduate School of Science and Technology, Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasakigosyokaido-cho, Sakyo-ku, Kyoto, Japan.
9
Department of Bacteriology and Virology, Osaka-City University Graduate School of Medicine, Osaka, Japan.
10
Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, 5-1-1 Toneyama, Toyonaka, Osaka, Japan.
11
Graduate School of Health Care Sciences, Jikei Institute, Osaka, Japan.
12
Central Laboratory, Japan BCG Laboratory, Kiyose-shi, Tokyo, Japan.

Abstract

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.

PMID:
30359374
PMCID:
PMC6201868
DOI:
10.1371/journal.pone.0204160
[Indexed for MEDLINE]
Free PMC Article

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