Abstract
BackgroundMycobacterium tuberculosis (MTB) is a common bacterium causing tuberculosis and remains a major pathogen for mortality. Although the MTB genome has been extensively explored for two decades, the functions of 27% (1051/3906) of encoded proteins have yet to be determined and these proteins are annotated as hypothetical proteins.MethodsWe assigned functions to these hypothetical proteins using SSEalign, a newly designed algorithm utilizing structural information. A set of rigorous criteria was applied to these annotations in order to examine whether they were supported by each parameter. Virulence factors and potential drug targets were also screened among the annotated proteins.ResultsFor 78% (823/1051) of the hypothetical proteins, we could identify homologs in Escherichia coli and Salmonella typhimurium by using SSEalign. Functional classification analysis indicated that 62.2% (512/823) of these annotated proteins were enzymes with catalytic activities and most of these annotations were supported by at least two other independent parameters. A relatively high proportion of transporter was identified in MTB genome, indicating the potential frequent transportation of frequent absorbing essential metabolites and excreting toxic materials in MTB. Twelve virulence factors and ten vaccine candidates were identified within these MTB hypothetical proteins, including two genes (rpoS and pspA) related to stress response to the host immune system. Furthermore, we have identified six novel drug target candidates among our annotated proteins, including Rv0817 and Rv2927c, which could be used for treating MTB infection.ConclusionsOur annotation of the MTB hypothetical proteins will probably serve as a useful dataset for future MTB studies.
Highlights
Mycobacterium tuberculosis (MTB) is a common bacterium causing tuberculosis and remains a major pathogen for mortality
Sequence similarity between MTB and other bacteria The 3906 coding proteins of MTB genome could be divided into 1051 Hypothetical protein (HP) and 2855 proteins with known functions
We found that the MTB HPs can be found with 245 and 234 best hits in E. coli and S. typhimurium, respectively (Fig. 1)
Summary
Mycobacterium tuberculosis (MTB) is a common bacterium causing tuberculosis and remains a major pathogen for mortality. In MTB, some of these HPs have been experimentally characterized, e.g. Rv0079, which was found to be a DosR regulon playing an inhibitory role in protein synthesis and interacting with TLR2 to promote cytokine secretion [9, 10]. Another example is Rv3873, which was identified to be a PE/PPE family protein that may play crucial roles in the MTB survival in different environments [11].
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