Early secreted antigenic target of 6 kda-like proteins of mycobacterium tuberculosis: Diagnostic and vaccine relevance

Abstract

Background: Early secreted antigenic target of 6 kDa (ESAT6) is low-molecular-weight and immunodominant protein of Mycobacterium tuberculosis with relevance to diagnosis and vaccine development. Analysis of the M. tuberculosis genome has shown the existence of 23 ESAT6-like genes. This study was aimed to determine M. tuberculosis-specificity vis-à-vis crossreactivity of ESAT6-like genes and encoded proteins and their potential in the diagnosis and vaccine development. Methods: All ESAT6-like proteins were characterized using the webserver Tuberculist. The sequence identities were determined using basic local alignment search tool. Results: The genes for six ESAT6-like proteins were located in M. tuberculosis-specific genomic regions of differences (RDs), i.e., EsxA and EsxB in RD1, EsxO and EsxP in RD7, and EsxV and EsxW in RD9. The genes for other ESAT6-like proteins were located in the genomic regions shared with other mycobacteria. Based on sequence identities, the ESA6-like proteins were divided into four subfamilies of 15 proteins and no subfamily of 8 proteins. The members of subfamilies 1-4 shared extensive sequence identities among the members of each subfamily. Each member of subfamily 1 (EsxI, EsxL, EsxN, EsxO, EsxV) and subfamily 2 (EsxJ, EsxK, EsxM, EsxP, EsxW) were homologs. Hence, the gene sequences identical to EsxO and EsxP located in RD7, and EsxV and EsxW located in RD9 were also present in the regions of M. tuberculosis genome shared with other mycobacteria. Conclusion: Because of their specificity to M. tuberculosis, only EsxA (ESAT6) and EsxB (CFP10) will be useful in the specific diagnosis. However, other ESAT6-like proteins may be useful for vaccine development against tuberculosis.

Keywords

• diagnosis
• early secreted antigenic target of 6 kda-like proteins
• sequence identity
• subfamilies
• vaccine