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Cell Rep. 2014 Dec 24;9(6):2317-29. doi: 10.1016/j.celrep.2014.11.023. Epub 2014 Dec 11.

Mycobacterium tuberculosis proteome microarray for global studies of protein function and immunogenicity.

Author information

1
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
2
National Key Laboratory of Biomacromolecules, Key Laboratory of Non-Coding RNA and Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; TB Healthcare Biotechnology Co., Ltd., Foshan, Guangdong 528000, China.
3
Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China.
4
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education); State Key Laboratory of Oncogenes and Related Genes; and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
5
National Key Laboratory of Biomacromolecules, Key Laboratory of Non-Coding RNA and Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
6
Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430071, China.
7
Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
8
Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education); State Key Laboratory of Oncogenes and Related Genes; and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: taosc@sjtu.edu.cn.
9
National Key Laboratory of Biomacromolecules, Key Laboratory of Non-Coding RNA and Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: zhangxe@sun5.ibp.ac.cn.

Abstract

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.

PMID:
25497094
DOI:
10.1016/j.celrep.2014.11.023
[Indexed for MEDLINE]
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