INVESTIGATION OF ACCD3 GENE OF MYCOBACTERIUM TUBERCULOSIS IRAQI ISOLATES

  • Asra'a A Abdul Jalil Department of Clinical Laboratory Science, College of Pharmacy, University of Anbar, Ramadi, Iraq.
  • Zahra M Al-khafaji Department of Genetic Engineering, Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, University of Baghdad, Baghdad, Iraq.
  • Mushtak T Al-ouqaili Department of Clinical Laboratory Science, College of Pharmacy, University of Anbar, Ramadi, Iraq.

Abstract

Objective: Mycobacterium tuberculosis, one of the deadliest human pathogens, causes several million new infections and about 2 million fatalities annually. The cell wall of M. tuberculosis is endowed with a highly impermeable, complex array of diverse lipids such as mycolic acids, which bestow the bacterium with not only virulence but also resistance to host immunity and antibiotics.

Methods: Mycobacterial lipid metabolism has thus emerged as an attractive target for the design and development of novel antimycobacterial therapeutics. The first committed step in the biosynthesis of mycolic acid is the carboxylation of acetyl-CoA to malonyl-CoA which is catalyzed by acetyl-coenzyme A carboxylase carboxyl transferase beta subunit (accD3), a primer pairs were designed computationally and used for the amplification of accD3 gene using conventional polymerase chain reaction (PCR) and sequencing the PCR product and analyze the results.

Results: Two sequences of the detection gene (LprM gene) and eight sequences of accD3 gene under study were deposited at NCBI – GenBank database with accession numbers (LC009881, LC009880.1, LC006979, LC008196, LC009412, LC009414, LC034168, LC038020, LC041163, and LC041368) and primer pairs deposited at Probe database/NCBI with accession number Pr032816836.

Conclusion: AccD3 gene is a good drug target in MDR M. tuberculosis strains.

Keywords: Tuberculosis, AccD3gene, Mycolic acid, Primer design, BLAST distance tree.

References

1. Earl EA, Altaf M, Murikoli RV, Swift S, O’Toole R. Native new Zealand plants with inhibitory activity towards Mycobacterium tuberculosis. BMC Complementary Altern Med 2010;10:2-7.
2. Ministry of Health of Iraq. New diagnosis of Tuberculosis in Iraq. Baghdad, Iraq: Tech. Rep., Ministry of Health of Iraq; 2012.
3. Polyak SW, Abell AD, Wilce MC, Zhang L, Booker GW. Structure, function and selective inhibition of bacterial acetyl-coa carboxylase. Appl Microbiol Biotechnol 2012;93:983-92.
4. UniProt Consortium. Activities at the universal protein resource (UniProt). Nucleic Acids Res 2014;42:D191-8.
5. Thomas SM, Kothia A, Chandrakar J, Pawar B, Bargaje MA. COST of therapy incurred for tuberculosis patients receiving directly observed therapy (DOT). Int J Pharm Pharm Sci 2015;7:141-4.
6. Takayama K, Wang C, Besra GS. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 2005;18:81-101.
7. Huard SB, Lazzarini JL, Ray W. PCR-based method to differentiate the subspecies of the Mycobacterium tuberculosis complex on the basis of genomic deletions. J Clin Microbiol 2013;41:1637-40.
8. Van Helden D, Thomas C, Robin M, Eileen G. Isolation of DNA from Mycobacterium tuberculosis. Methods in Molecular Medicine, Mycobacterium Tuberculosis Protocols Vol. 54. Canada: John Wiley & Sons; 2001.
9. Abdul-Jalil ZM, Al-Khafaji A, Mankhi Z, Ali AR, Al-Ani M. Study of LprM gene in Iraqi Mycobacterium tuberculosis isolates. World J Pharm Pharm Sci 2014;3:142-51.
10. Holton SJ, King-Scott S, Nasser Eddine A, Kaufmann SH, Wilmanns M. Structural diversity in the six-fold redundant set of acyl-coA carboxyltransferases in Mycobacterium tuberculosis. FEBS Lett 2006;580:6898-902.
11. Noll H, Bloch H. Studies on the chemistry of the cord factor of Mycobacterium tuberculosis. J Biol Chem 1955;224:149-63.
12. Gago G, Kurth D, Diacovich L, Tsai S, Gramajo H. Biochemical and Structural characterization of an essential acyl coenzyme a carboxylase from Mycobacterium tuberculosis. J Bacteriol 2006;188:477-86.
13. Gibson GR, Brown K, Krumbach A, Dover K, Sahm L, Shioyama H, et al. Acyl-CoA carboxylases (accD2 and accD3) together with a unique polyketide synthase (Cg-pks) are key to mycolic acid biosynthesis in corynebacterianeae like Corynebacteriumglutamicum and Mycobacterium tuberculosis. J Biol Chem 2004;151:1-47.
14. Shaji J, Shaikh M. Drug-resistant tuberculosis: Recent approach in polymer based nanomedicine. Int J Pharm Pharm Sci 2016;8:1-6.
15. Stecher TK, Peterson G, Filipski AD, Kumar S. MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013;30:2725 9.
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Jalil, A. A. A., Z. M. Al-khafaji, and M. T. Al-ouqaili. “INVESTIGATION OF ACCD3 GENE OF MYCOBACTERIUM TUBERCULOSIS IRAQI ISOLATES”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 8, Aug. 2018, pp. 208-11, doi:10.22159/ajpcr.2018.v11i8.25269.
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