Comparative genomic and proteomic analyses of PE/PPE multigene family of Mycobacterium tuberculosis H ₃₇Rv and H ₃₇Ra reveal novel and interesting differences with implications in virulence

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease taking one human life every 15 s globally. The two well-characterized strains H ₃₇Rv and H ₃₇Ra, derived from the same parental strain M. tuberculosis H ₃₇, show dramatically different pathogenic phenotypes. PE/PPE gene family, comprising of 176 open reading frames and present exclusively in genus Mycobacterium, accounts for ∼10% of the M. tuberculosis genome. Our comprehensive in silico analyses of PE/PPE family of H ₃₇Ra and virulent H ₃₇Rv strains revealed genetic differences between these strains in terms of several single nucleotide variations and InDels and these manifested in changes in physico-chemical properties, phosphorylation sites, and protein: protein interacting domains of the corresponding proteomes. Similar comparisons using the 13 sigma factor genes, 36 members of the mammalian cell entry family, 13 mycobacterial membrane protein large family members and 11 two-component signal transduction systems along with 5 orphaned response regulators and 2 orphaned sensor kinases failed to reveal very significant difference between H ₃₇Rv and H ₃₇Ra, reinforcing the importance of PE/PPE genes. Many of these changes between H ₃₇Rv and H ₃₇Ra can be correlated to differences in pathogenesis and virulence of the two strains.