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September 20-21, 2017 | Philadelphia, USA
Global summit on
TUBERCULOSIS AND LUNG DISEASE
alliedacademies
Int J Respir Med 2017 Volume 2 Issue 2
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.
tb), takes one human life every 15-20 seconds globally. We
have been focusing on the functional biology of this pathogen
with a view to design innovative interventions against TB. We
identified and characterized several virulent proteins of M.
tb that help in intracellular survival by modifying host cellular
machinery. Phylogenetic analysis of M. tb methyltransferases
(MTases) pointed to an evolutionary relationship of M. tb with
halotolerant organisms, notably in the context of their ability
to withstand the host osmotic stress, thus highlighting their
likely role in pathogenesis, virulence and niche adaptation.
Some of the MTases exhibit antigenic patches and regulate
transmembrane transport proteins. Another class of proteins,
the sigma factors and their target genes, has been shown to
move from non-pathogenic to pathogenic Mycobacteria. The
M. tb PE_PGRS subfamily has unusually high levels of disordered
stretches compared to any other family in the proteome and
was highly enriched in average number of anchor binding sites,
eukaryotic linear motifs (ELMs) and has highly biased amino
acid composition rich in disorder promoting alanine and glycine
residues and play roles in molecular mimicry. One member
of this protein family causes activation of Unfolded Protein
Response as evident from increased expression of GRP78/
GRP94 and CHOP/ATF4, leading to disruption of intracellular
Ca2+ homeostasis and increased NO and ROS production.
The consequent activation of effector caspase-8, resulted in
apoptosis of macrophages. In other series of investigations,
comparative proteomic and genomic analyses revealed the
exclusive presence of ‘Signature sequences’ in M. tb genome,
some of which have potential utility in TB diagnosis based
on limited clinical validation. Hypothetical proteins coded by
one such ‘Signature sequences’ was found to be a functional
S-adenosyl dependent DNA methyltransferase and binds DNA
non-specifically and protects DNA from oxidative stress by
scavenging iron thereby, preventing generation of free radicals
and by physically binding DNA and providing a physical barrier.
Using drug re-purposing strategies we also identified existing
US FDA approved drugs that inhibit M. tb by disrupting the
pathogen’s biofilm forming ability and thus have the potential
to act as a newTB drug and to reduce the duration of treatment.
My presentation will cover some of these findings from our
group.
Speaker Biography
Seyed Ehtesham Hasnain is a Professor and the Head of Jamia Hamdard-Institute of
Molecular Medicine and Invited Professor at Indian Institute of Technology, Delhi. He
has received his PhD from JNU (1980), Post-doctoral training in Canada/USA, and was
a Staff Scientist at National Institute of Immunology, New Delhi and the Vice Chancel-
lor (President) of Jamia Hamdard. He is associated with editorial boards of national/
international journals and has authored more than 250 publications/patents and recip-
ient of many national and international awards including S S Bhatnagar Prize, Ranbaxy
Research Award, J C Bose National Fellow, Humboldt Research Prize and Robert Koch
Fellow (Berlin). He is an Elected Fellow of German Academy of Sciences, Leopoldina
and American Academy of Microbiology, etc. He has received Germany’s highest rec-
ognition DasVerdienstkreuz, 1. Klasse in 2014. His research area includes functional
molecular epidemiology and biology, Mycobacterium tuberculosis, transcriptional
regulation of gene expression, genetic hyper-variability, molecular pathogenesis and
disease intervention.
e:
Seyed Ehtesham Hasnain
Jamia Hamdard University, India
Newer molecular targets and therapeutic strategies for intervention against
Mycobacterium tuberculosis