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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / immunology*
  • Binding Sites
  • Case-Control Studies
  • Circular Dichroism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / immunology*
  • Female
  • Humans
  • Immunoglobulin G / metabolism*
  • Male
  • Middle Aged
  • Models, Molecular
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Secondary
  • Tuberculosis / diagnosis*
  • Young Adult


  • Bacterial Proteins
  • DNA-Binding Proteins
  • Immunoglobulin G
  • MDP1 protein, Mycobacterium

Grant support

This work was supported by the Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research (, Grant numbers 16H05187 (S.M.), 17K08823(A.N), 16K08774(Y.O); by the Japan Agency for Medical Research and Development, grant JP18fk0108005 to Prof. Sohkichi Matsumoto; and by The United States–Japan Cooperative Medical Science Program against Tuberculosis and Leprosy to Sohkichi Matsumoto. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.