Tuberculosis, an ancient, yet re-emerging infectious disease, is responsible for more deaths than almost all other infectious diseases, and the vaccine, drugs and diagnostic tests currently in use are limiting the effectiveness of global efforts to prevent and control TB. The BCG vaccine, the only licensed TB vaccine available, has now been in use for almost one hundred years; however, it provides only limited protection. Drugs currently used to treat TB have been in use clinically for almost half a century and bacterial drug resistance is a growing problem. In addition, current methods for detecting TB are not very effective, and the detection rate is low. Suitable biomarkers which can be used in rapid screening methods for TB are lacking.

Chinese scientists and clinical experts from the CAS Institute of Biophysics, Shanghai Jiao Tong University, the CAS Wuhan Institute of Virology, the Center for Tuberculosis Control of Guangdong Province, the CAS Institute of Hydrobiology, the Shanghai Municipal Center for Disease Control and Prevention, and TB Health care Biotechnology Co., Ltd., have worked together to construct the first Mycobacterium tuberculosis (MTB) proteome microarray, a powerful high-throughput experimental platform for basic research on TB, and published the results from their joint study in the journal Cell Reports on 11th Dec., 2014.

The MTB proteome microarray includes the products of 4262 Mycobacterium tuberculosis open-reading frames and covers 95% of the proteome. It can be used for global analysis of protein-protein interactions in studies of the interactions between human immune cells and the MTB pathogen, for analysis of protein interactions with small moleculesin the global discovery of drug targets, and for high-throughput analysis of serum samples in the systematic discovery of biomarkers for use in the diagnosis of tuberculosis. The MTB proteome microarrayis thus a suitable tool for enabling the systematic discovery of new immunogens and biomarkers, and will likely facilitate the development of new and efficient vaccines, drugs and diagnostic technology.

In studies to demonstrate typical applications of the proteome microarray, PknG, a protein kinase, and c-di-GMP, a small molecule that is a ubiquitous second messenger in bacteria, were found to interact with many previously unreported protein binding partners. Results indicated that both PknG phosphorylation and c-di-GMP are involved in the regulation of the MTB rhamnose synthesis pathway, an important pathway in cell wall biosynthesis. In addition, analysis of serum samples using the proteome microarray identified a panel of 14 biomarkers than can effectively distinguish between patients with active TB and those who have recovered from the disease, and thus has potential as an index for monitoring treatment outcome.

This collaborative study took five years to complete and was supported by grants from the Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health, the Chinese Academy of Sciences, the National High Technology Research and Development Program of China, and the National Natural Science Foundation of China.