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  1. Trends in Bioinformatics
  2. Vol 7 (1), 2014
  3. 19-26

Trends in Bioinformatics

Year: 2014 | Volume: 7 | Issue: 1 | Page No.: 19-26
Research Article

In silico Analysis of Essential Tricarboxylic Acid Cycle Enzymes from Biofilm-forming Bacteria

M.F.Z.R. Yahya
Faculty of Applied Sciences, Universiti Teknologi MARA Shah Alam, 40450, Shah Alam, Selangor, Malaysia

U.M.A. Hamid
Faculty of Applied Sciences, Universiti Teknologi MARA Shah Alam, 40450, Shah Alam, Selangor, Malaysia

M.Y. Norfatimah
Faculty of Applied Sciences, Universiti Teknologi MARA Shah Alam, 40450, Shah Alam, Selangor, Malaysia

R. Kambol
Faculty of Applied Sciences, Universiti Teknologi MARA Shah Alam, 40450, Shah Alam, Selangor, Malaysia

The Tricarboxylic Acid Cycle (TCA) cycle is the central point in the metabolism of living organisms and is important for the survival of infectious biofilms. The inhibition of this vital point could be a promising strategy for the control of infectious biofilms. Therefore, this study was carried out to identify the potential drug targets from the TCA cycle of several Biofilm-Forming Bacteria (BFB) and to identify the available small molecule drugs against the TCA cycle enzymes. Based on thein silico substractive genomic approach, citrate lyase subunit alpha/citrate CoA-transferase [EC: 4.1.3.6], succinate dehydrogenase iron-sulfur subunit (EC: 1.3.99.1) and 2-oxoglutarate ferredoxin oxidoreductase subunit delta [EC: 1.2.7.3] were found to be essential and exclusively present in the BFB. Further in silicoanalyses showed that most of them are chemically regulated by myristoylation, phosphorylation, glycosylation and amidation. Based on the sequence search against DrugBank database, the potential small molecule drugs for biofilm treatment are 2-[1-methylhexyl]-4, 6-dinitrophenol, Atpenin A5 and Ubiquinone-2 which all target the succinate dehydrogenase enzyme of BFB. This study demonstrates the rapid identification of potential drug targets and small molecule drugs which could be useful in biofilm control strategies.
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References


  1. Resch, A., R. Rosenstein, C. Nerz and F. Gotz, 2005.Differential gene expression profiling ofStaphylococcus aureus cultivated under biofilm and planktonic conditions. Applied Environ. Microbiol., 71: 2663-2676.
    CrossRefDirect Link

  2. Mack, D.M., W. Fischer, A. Krokotsch, K. Leopold, R. Hartmann, H. Egge and R. Laufs, 1996.The intercellular adhesin involved in biofilm accumulation ofStaphylococcus epidermidis is a linear-1, 6-linked glucosaminoglycan: Purification and structural analysis. J. Bacteriol., 178: 175-183.

  3. Barh, D. and A. Kumar, 2009.In silico identification of candidate drug and vaccine targets from various pathways inNeisseria gonorrhoeae.In silico Biol., 9: 225-231.
    CrossRefDirect Link

  4. Kim, H.J., A. Roux and A.L. Sonenshein, 2002.Direct and indirect roles of CcpA in regulation ofBacillus subtilis krebs cycle genes. Mol. Microbiol., 45: 179-190.
    CrossRefDirect Link

  5. Mikkelsen, H., Z. Duck, K. S. Lilley and M. Welch, 2007.Interrelationships between Colonies, biofilms and planktonic cells ofPseudomonas aeruginosa. J. Bacteriol., 189: 2411-2416.
    CrossRefDirect Link

  6. Miyadera, H., K. Shiomi, H. Ui, Y. Yamaguchi and R. Masumaet al., 2003.Atpenins, potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase). Proc. Natl. Acad. Sci. USA., 100: 473-477.
    CrossRefDirect Link

  7. Ogata, H., S. Goto, K. Sato, W. Fujibuchi, H. Bono and M. Kanehisa, 1999.KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 27: 29-34.
    Direct Link

  8. Xu, H., K. Teo, H. Neo and Y. Liu, 2012.Chemically inhibited ATP synthesis promoted detachment of different-age biofilms from membrane surface. Applied Microbiol. Biotechnol., 95: 1073-1082.
    CrossRefDirect Link

  9. Potapova, I.A., M.R. El-Maghrabi, S.V. Doronin and W.B. Benjamin, 2000.Phosphorylation of recombinant human ATP: Citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP: Citrate lyase by phosphorylated sugars. Biochemistry, 39: 1169-1179.
    CrossRefDirect Link

  10. Kohanski, M.A., D.J. Dwyer, B. Hayete, C.A. Lawrence and J.J. Collins, 2007.A common mechanism of cellular death induced by bactericidal antibiotics. Cell, 130: 797-810.
    CrossRefDirect Link

  11. Broncel, M., A.J. Falenski, C.S. Wagner, P.R.C. Hackenberger and B. Koksch, 2010.How post-translational modifications influence amyloid formation: A systematic study of phosphorylation and glycosylation in model peptides. Chem. Eur. J., 16: 7881-7888.
    CrossRefDirect Link

  12. Sadykov, M.R., T. Hartmann, T.A. Mattes, M. Hiatt and N.J. Jannet al., 2011.CcpA coordinates central metabolism and biofilm formation inStaphylococcus epidermidis. Microbiology, 157: 3458-3468.
    CrossRefDirect Link

  13. Salvi, M., N.A. Morrice, A.M. Brunati and A. Toninello, 2007.Identification of the flavoprotein of succinate dehydrogenase and aconitase asin vitro mitochondrial substrates of Fgr tyrosine kinase. FEBS Lett., 581: 5579-5585.

  14. Hulo, N., A. Bairoch, V. Bulliard, L. Cerutti and E. De Castroet al., 2006.The PROSITE database. Nucleic Acids Res., 34: D227-D230.
    PubMedDirect Link

  15. Renslow, R.S., J.T. Babauta, A.C. Dohnalkova, M.I. Boyanov and K.M. Kemneret al., 2013.Metabolic spatial variability in electrode-respiringGeobacter sulfurreducens biofilms. Energy Environ. Sci., 6: 1827-1836.
    CrossRefDirect Link

  16. Zhang, R., H.Y. Ou and C.T. Zhang, 2004.DEG: A database of essential genes. Nucleic Acids Res., 32: D271-D272.
    CrossRefPubMedDirect Link

  17. Altschul, S.F., W. Gish, W. Miller, E.W. Myers and D.J. Lipman, 1990.Basic local alignment search tool. J. Mol. Biol., 215: 403-410.
    CrossRefPubMedDirect Link

  18. Morya, V.K., V. Dewaker, S.D. Mecarty and R. Singh, 2010.In silico analysis of metabolic pathways for identification of putative drug targets forStaphylococcus aureus. J. Comput. Sci. Syst. Biol., 3: 62-69.
    CrossRef

  19. Law, V., C. Knox, Y. Djoumbou, T. Jewison and A.C. Guoet al., 2014.DrugBank 4.0: Shedding new light on drug metabolism. Nucleic Acids Res., 42: 1091-1097.

  20. Pishchik, V.N., I.I. Cherniaeva, E.A. Semenova, E.I. Bel'kova, N.R. Vasser, G.N. Koval and A.I. Turianitsa, 1997.Features of metabolism ofKlebsiella genus bacteria. Mikrobiologiia, 66: 54-59.
    PubMed

  21. Sharma, V., P. Gupta and A. Dixit, 2008.In silico identification of putative drug targets from different metabolic pathways ofAeromonas hydrophila.In silico Biol., 8: 331-338.
    PubMedDirect Link
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