title: Mycobacterium tuberculosis proteome microarray for global studies of protein function and immunogenicity.
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.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jiaoyu
authors.initials: J
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Lijun
authors.initials: L
authors.lastname: Bi
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Shu-juan
authors.initials: SJ
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Joy
authors.initials: J
authors.lastname: Fleming
authors.affiliation: 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.
authors.forename: He-wei
authors.initials: HW
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Gu
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: 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.
authors.forename: Zong-xiu
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Rui-ping
authors.initials: RP
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jing-fang
authors.initials: JF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Xude
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Tuberculosis Control of Guangdong Province, Guangzhou 510630, China.
authors.forename: Haicheng
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ge
authors.affiliation: Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Hai-nan
authors.initials: HN
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Fan-lin
authors.initials: FL
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Dianbing
authors.initials: D
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Haiying
authors.initials: H
authors.lastname: Hang
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.affiliation: 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.
authors.forename: Sheng-ce
authors.initials: SC
authors.lastname: Tao
authors.affiliation: 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.
authors.forename: Xian-en
authors.initials: XE
authors.lastname: Zhang
mesh_terms: D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames; D040081:Protein Array Analysis; D020543:Proteome / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D020543:Proteome