Cell Reports (Dec 2014)

Mycobacterium Tuberculosis Proteome Microarray for Global Studies of Protein Function and Immunogenicity

  • Jiaoyu Deng,
  • Lijun Bi,
  • Lin Zhou,
  • Shu-juan Guo,
  • Joy Fleming,
  • He-wei Jiang,
  • Ying Zhou,
  • Jia Gu,
  • Qiu Zhong,
  • Zong-xiu Wang,
  • Zhonghui Liu,
  • Rui-ping Deng,
  • Jing Gao,
  • Tao Chen,
  • Wenjuan Li,
  • Jing-fang Wang,
  • Xude Wang,
  • Haicheng Li,
  • Feng Ge,
  • Guofeng Zhu,
  • Hai-nan Zhang,
  • Jing Gu,
  • Fan-lin Wu,
  • Zhiping Zhang,
  • Dianbing Wang,
  • Haiying Hang,
  • Yang Li,
  • Li Cheng,
  • Xiang He,
  • Sheng-ce Tao,
  • Xian-En Zhang

DOI
https://doi.org/10.1016/j.celrep.2014.11.023
Journal volume & issue
Vol. 9, no. 6
pp. 2317 – 2329

Abstract

Read online

Poor understanding of the basic biology of Mycobacterium tuberculosis (MTB), the etiological agent of tuberculosis, hampers development of much-needed drugs, vaccines, and diagnostic tests. Better experimental tools are needed to expedite investigations of this pathogen at the systems level. Here, we present a functional MTB proteome microarray covering most of the proteome and an ORFome library. We demonstrate the broad applicability of the microarray by investigating global protein-protein interactions, small-molecule-protein binding, and serum biomarker discovery, identifying 59 PknG-interacting proteins, 30 bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding proteins, and 14 MTB proteins that together differentiate between tuberculosis (TB) patients with active disease and recovered individuals. Results suggest that the MTB rhamnose pathway is likely regulated by both the serine/threonine kinase PknG and c-di-GMP. This resource has the potential to generate a greater understanding of key biological processes in the pathogenesis of tuberculosis, possibly leading to more effective therapies for the treatment of this ancient disease.