Identification and characterization of a major cell wall-associated iron-regulated envelope protein (Irep-28) in

Veena C Yeruva1, Sridevi Duggirala, V Lakshmi

  • 1School of Life Sciences, University of Hyderabad, Hyderabad-500 046, India.

Insights

Iron regulates the expression of mycobactin and carboxymycobactin siderophores in Mycobacterium tuberculosis. A cell wall protein, HupB, is identified as iron-regulated and a potential drug target for tuberculosis.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Immunology

Background:

  • Iron is essential for Mycobacterium tuberculosis growth and virulence.
  • Expression of mycobactin and carboxymycobactin siderophores is known to be iron-regulated.
  • The role of other iron-regulated proteins in M. tuberculosis remains to be fully elucidated.

Purpose of the Study:

  • To investigate the coordinate regulation of siderophore expression by iron in M. tuberculosis.
  • To identify and characterize novel iron-regulated proteins involved in M. tuberculosis physiology.
  • To assess the potential of identified iron-regulated proteins as drug targets.

Main Methods:

  • Analysis of siderophore expression under varying iron conditions.
  • Identification and characterization of iron-regulated proteins using proteomic and genetic approaches.
  • Antibody detection in patient sera to assess protein relevance.

Main Results:

  • Iron was found to regulate the coordinate expression of mycobactin and carboxymycobactin.
  • A 28-kDa cell wall-associated iron-regulated protein (Irep-28) was identified.
  • Irep-28 was characterized as the DNA-binding HU homologue HupB protein (hupB [Rv2986c]).
  • Antibodies against HupB were detected in sera from tuberculosis patients.

Conclusions:

  • HupB is an iron-regulated protein in M. tuberculosis, involved in siderophore expression.
  • The cell wall localization of HupB suggests its potential as a drug target.
  • Detection of anti-HupB antibodies indicates its immunogenic potential in tuberculosis patients.