AsianScientist (Jan. 30, 2015) – The entire proteome of an ancient enemy has now been sequenced and made available online. The proteome microarray of Mycobacterium tuberculosis, the causative agent of tuberculosis, would help scientists find urgently needed new drugs and vaccines. The study documenting the project has been published in Cell Reports.
Tuberculosis (TB), an ancient yet re-emerging infectious disease, is responsible for more deaths than almost all other infectious diseases. However the vaccine, drugs and diagnostic tests currently in use are reaching their limits in terms of their effectiveness in global efforts to prevent and control TB.
The Bacillus Calmette–Guérin (BCG) vaccine, the only licensed TB vaccine, 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 Chinese Academy of Sciences (CAS) Wuhan Institute of Virology, Institute of Biophysics and Institute of Hydrobiology, Shanghai Jiao Tong University, the Center for Tuberculosis Control of Guangdong Province, the Shanghai Municipal Center for Disease Control and Prevention, and TB Healthcare 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.
The MTB proteome microarray includes the products of 4,262 Mycobacterium tuberculosis open-reading frames and covers 95 percent 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 molecules in 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 microarray provides researchers with a 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.
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.
The article can be found at: Deng et al. (2014) Mycobacterium Tuberculosis Proteome Microarray for Global Studies of Protein Function and Immunogenicity.
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Source: Chinese Academy of Sciences; Photo: NIAID/Flickr/CC.
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