Identification of Missing Carbon Fixation Enzymes as Potential Drug Targets in Mycobacterium Tuberculosis

Journal of Integrative Bioinformatics
Amit KatiyarKrishna Kant Azad

Abstract

Metabolic adaptation to the host environment has been recognized as an essential mechanism of pathogenicity and the growth of Mycobacterium tuberculosis (Mtb) in the lungs for decades. The Mtb uses CO2 as a source of carbon during the dormant or non-replicative state. However, there is a lack of biochemical knowledge of its metabolic networks. In this study, we investigated the CO2 fixation pathways (such as ko00710 and ko00720) most likely involved in the energy production and conversion of CO2 in Mtb. Extensive pathway evaluation of 23 completely sequenced strains of Mtb confirmed the existence of a complete list of genes encoding the relevant enzymes of the reductive tricarboxylic acid (rTCA) cycle. This provides the evidence that an rTCA cycle may function to fix CO2 in this bacterium. We also proposed that as CO2 is plentiful in the lungs, inhibition of CO2 fixation pathways (by targeting the relevant CO2 fixation enzymes) could be used in the expansion of new drugs against the dormant Mtb. In support of the suggested hypothesis, the CO2 fixation enzymes were confirmed as a potential drug target by analyzing a number of attributes necessary to be a good bacterial target.

References

Jun 1, 1991·Infection and Immunity·P AndersenI Heron
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Oct 1, 1996·Tubercle and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·R Ohman, M Ridell
Feb 13, 2001·Trends in Pharmacological Sciences·G C Terstappen, A Reggiani
Dec 18, 2002·Journal of Bacteriology·Sae W ParkYoung M Kim
Jun 1, 1955·Journal of Bacteriology·W B SCHAEFERG MIDDLEBROOK
Dec 4, 2003·Biochemical and Biophysical Research Communications·Masahiro YamamotoYasuo Igarashi
Jul 26, 2005·Infection and Immunity·K Heran Darwin, Carl F Nathan
Dec 22, 2005·Infection and Immunity·Shuangping Shi, Sabine Ehrt
Dec 31, 2005·Nucleic Acids Research·David S WishartJennifer Woolsey
Feb 28, 2006·The Biological Bulletin·Vijayasarathy Srinivasan, Harold J Morowitz
May 9, 2006·Cell Biochemistry and Biophysics·Nelson José Freitas da SilveiraWalter Filgueira de Azevedo
Feb 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·Robert Van der GeizeLindsay D Eltis
May 17, 2007·Current Molecular Medicine·Simon J Waddell, Philip D Butcher
May 29, 2007·Nucleic Acids Research·Yuki MoriyaMinoru Kanehisa
Jul 28, 2007·BMC Infectious Diseases·Dennis J Murphy, James R Brown
Dec 1, 2007·Nucleic Acids Research·David S WishartMurtaza Hassanali
May 14, 2008·Cell Host & Microbe·Michael U ShilohJeffery S Cox
Oct 17, 2008·The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien Des Maladies Infectieuses Et De La Microbiologie Médicale·Paul E Alexander, Prithwish De
Dec 20, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mathieu DesmardJorge Boczkowski
Nov 7, 2009·Extremophiles : Life Under Extreme Conditions·Masahiro YamamotoYasuo Igarashi
May 11, 2010·Nature Reviews. Microbiology·Ivan A BergGeorg Fuchs
Nov 10, 2010·Nucleic Acids Research·Craig KnoxDavid S Wishart
Mar 4, 2011·Current Medicinal Chemistry·G Heberlé, W F de Azevedo
Mar 4, 2011·Current Medicinal Chemistry·Walter Filgueira de Azevedo
Nov 26, 2011·Nucleic Acids Research·María P MagariñosFernán Agüero
Dec 19, 2012·Medical Gas Research·Vineetha M Zacharia, Michael U Shiloh
Nov 10, 2013·Nucleic Acids Research·Vivian LawDavid S Wishart
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Jan 24, 2014·Bioinformatics·Philip JonesSarah Hunter
Aug 5, 2015·Current Drug Targets·Rohit SharmaAnil K Sharma
Sep 7, 2016·Yonsei Medical Journal·Shinwon LeeIhm Soo Kwak

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EMBOSS explorer
BLAST
Perl script
Basic Local Alignment Search Tool ( BLAST )

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