Integrative analysis of transcriptome and genome indicates two potential genomic islands are associated with pathogenesis of Mycobacterium tuberculosis.

ABSTRACT

Mycobacterium tuberculosis (M.tb) is a successful human pathogen and widely prevalent throughout the world. Genomic islands (GIs) are thought to be related to pathogenicity. In this study, we predicted two potential genomic islands in M.tb genome, respectively named as GI-1 and GI-2. It is indicated that the genes belong to PE_PGRS family in GI-1 and genes involved in sulfolipid-1 (SL-1) synthesis in GI-2 are strongly associated with M.tb pathogenesis. Sequence analysis revealed that the five PGRS genes are more polymorphic than other PGRS members in full virulence M.tb complex strains at significance level 0.01 but not in attenuated strains. Expression analysis of microarrays collected from literatures displayed that GI-1 genes, especially Rv3508 might be correlated with the response to the inhibition of aerobic respiration. Microarray analysis also showed that SL-1 cluster genes are drastically down-expressed in attenuated strains relative to full virulence strains. We speculated that the effect of SL-1 on M.tb pathogenicity could be associated with long-term survival and persistence establishment during infection. Additionally, the gene Rv3508 in GI-1 was under positive selection. Rv3508 may involve the response of M.tb to the inhibition of aerobic respiration by low oxygen or drug PA-824, and it may be a common feature of genes in GI-1. These findings may provide some novel insights into M.tb physiology and pathogenesis.