Open AccessComparative Analyses of Nonpathogenic, Opportunistic, and Totally Pathogenic Mycobacteria Reveal Genomic and Biochemical Variabilities and Highlight the Survival Attributes of Mycobacterium tuberculosis
Author(s) -
Syed Asad Rahman,
Yadvir Singh,
Sandeep Kohli,
Javeed Ahmad,
Nasreen Z. Ehtesham,
Anil K. Tyagi,
Seyed E. Hasnain
Publication year - 2014
Publication title -
mbio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.562
H-Index - 121
eISSN - 2161-2129
pISSN - 2150-7511
DOI - 10.1128/mbio.02020-14
Subject(s) - biology , proteome , mycobacterium , mycobacterium tuberculosis , microbiology and biotechnology , genome , homology (biology) , gene , tuberculosis , virulence , mycobacterium bovis , genetics , bacteria , medicine , pathology
Mycobacterial evolution involves various processes, such as genome reduction, gene cooption, and critical gene acquisition. Our comparative genome size analysis of 44 mycobacterial genomes revealed that the nonpathogenic (NP) genomes were bigger than those of opportunistic (OP) or totally pathogenic (TP) mycobacteria, with the TP genomes being smaller yet variable in size—their genomic plasticity reflected their ability to evolve and survive under various environmental conditions. From the 44 mycobacterial species, 13 species, representing TP, OP, and NP, were selected for genomic-relatedness analyses. Analysis of homologous protein-coding genes shared betweenMycobacterium indicus pranii (NP),Mycobacterium intracellulare ATCC 13950 (OP), andMycobacterium tuberculosis H37Rv (TP) revealed that 4,995 (i.e., ~95%)M. indicaus pranii proteins have homology withM. intracellulare , whereas the homologies amongM. indicus pranii ,M. intracellulare ATCC 13950, andM. tuberculosis H37Rv were significantly lower. A total of 4,153 (~79%)M. indicus pranii proteins and 4,093 (~79%)M. intracellulare ATCC 13950 proteins exhibited homology with theM. tuberculosis H37Rv proteome, while 3,301 (~82%) and 3,295 (~82%)M. tuberculosis H37Rv proteins showed homology withM. indicus pranii andM. intracellulare ATCC 13950 proteomes, respectively. Comparative metabolic pathway analyses of TP/OP/NP mycobacteria showed enzymatic plasticity betweenM. indicus pranii (NP) andM. intracellulare ATCC 13950 (OP),Mycobacterium avium 104 (OP), andM. tuberculosis H37Rv (TP).Mycobacterium tuberculosis seems to have acquired novel alternate pathways with possible roles in metabolism, host-pathogen interactions, virulence, and intracellular survival, and by implication some of these could be potential drug targets.IMPORTANCE The complete sequence analysis ofMycobacterium indicus pranii , a novel species ofMycobacterium shown earlier to have strong immunomodulatory properties and currently in use for the treatment of leprosy, places it evolutionarily at the point of transition to pathogenicity. With the purpose of establishing the importance ofM. indicus pranii in providing insight into the virulence mechanism of tuberculous and nontuberculous mycobacteria, we carried out comparative genomic and proteomic analyses of 44 mycobacterial species representing nonpathogenic (NP), opportunistic (OP), and totally pathogenic (TP) mycobacteria. Our results clearly placedM. indicus pranii as an ancestor of theM. avium complex. Analyses of comparative metabolic pathways betweenM. indicus pranii (NP),M. tuberculosis (TP), andM. intracellulare (OP) pointed to the presence of novel alternative pathways inM. tuberculosis with implications for pathogenesis and survival in the human host and identification of new drug targets.