**2. Genetic architecture of Region of Difference-1 (RD-1)**

Comparative genome analysis using DNA microarray, bacterial artificial chromosomes (BAC) and the subtractive hybridization between virulent and attenuated strains of Mtb complex and *M. bovis* BCG identified several regions of difference (RD) (Behr et al., 1999; Gordon et al., 1999; Mahairas et al., 1996). A gene segment of 9.5kb that encompasses nine open reading frames (ORF) of Rv3871-Rv3879c is present in virulent strains of Mtb, and which is deleted consistently in all the strains of *M. bovis* BCG (Cole et al., 1998). This region was designated as RD-1. Two of these ORFs, Rv3874 and Rv3875, encode 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secreted antigenic target (ESAT-6) protein respectively. Interestingly, deletion of the RD-1 fragments from Mtb causes loss of its virulence, while introduction of the RD-1 locus into *M. bovis* BCG or *M. microti* resulted in increased virulence and survival properties (Behr, 2002; Pym et al., 2002; Lewis et al., 2003; Demangel et al., 2005). This review will focus on the role of these two proteins in modulation of the macrophage signaling pathways and macrophage functions for the bacteria to persist for longer time. We also discuss about the potential role of these proteins as vaccine candidates owing to their high immunogenicity.
