Since 1921, Mycobacterium bovis bacillus Calmette-Guérin (BCG) has been recognized as an important vaccine to prevent tuberculosis worldwide. Nonetheless, a global analysis of BCG proteome has not been clearly investigated. In this study, we performed an in-depth proteomic analysis of BCG under an in vitro cultivation condition using SDS-PAGE and high resolution Fourier transform mass spectrometry. In total, 3434 proteins (35,259 unique peptides) including 512 transmembrane proteins were identified, covering ~87% of the predicted BCG proteome. Seven pseudogene protein products were also obtained and validated by RT-PCR at gene transcript level. Additionally, translational start sites of 832 proteins were confirmed and 186 were extended using N-terminus-derived peptides. The physicochemical characteristics of all identified proteins were determined. Some predominant proteins, including PE and PPE family proteins, lipoproteins, heat shock proteins, transport proteins and low molecular weight protein antigens, are discussed, which represent potential prominent antigens in the humoral and cellular immune response. This study represents the most comprehensive BCG proteome to date, which will likely facilitate the design of vaccination and immunodiagnostic strategies against TB.
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