A Novel in Silico Approach to Identify Potential Therapeutic Targets in Human Bacterial Pathogens

Overview

Journal Hugo J

Publisher Springer

Specialty Genetics

Date 2012 Dec 4

PMID 23205162

Citations 15

Authors

Umashankar Vetrivel

Gurunathan Subramanian

Sudarsanam Dorairaj

Affiliations

Soon will be listed here.

Abstract

Unlabelled: In recent years, genome-sequencing projects of pathogens and humans have revolutionized microbial drug target identification. Of the several known genomic strategies, subtractive genomics has been successfully utilized for identifying microbial drug targets. The present work demonstrates a novel genomics approach in which codon adaptation index (CAI), a measure used to predict the translational efficiency of a gene based on synonymous codon usage, is coupled with subtractive genomics approach for mining potential drug targets. The strategy adopted is demonstrated using respiratory pathogens, namely, Streptococcus pneumoniae and Haemophilus influenzae as examples. Our approach identified 8 potent target genes (Streptococcus pneumoniae-2, H. influenzae-6), which are functionally significant and also play key role in host-pathogen interactions. This approach facilitates swift identification of potential drug targets, thereby enabling the search for new inhibitors. These results underscore the utility of CAI for enhanced in silico drug target identification.

Electronic Supplementary Material: The online version of this article (doi:10.1007/s11568-011-9152-7) contains supplementary material, which is available to authorized users.

Citing Articles

Structural and Functional Annotation and Molecular Docking Analysis of a Hypothetical Protein from : An In-Silico Approach.

Mazumder L, Rakibul Hasan M, Fatema K, Islam M, Tamanna S Biomed Res Int. 2022; 2022:4302625.

PMID: 36105928 PMC: 9467719. DOI: 10.1155/2022/4302625.

Pathogenomic in silico approach identifies NSP-A and Fe-IIISBP as possible drug targets in Neisseria Meningitidis MC58 and development of pharmacophores as novel therapeutic candidates.

Joshi M, Purohit M, Shah D, Patel D, Depani P, Moryani P Mol Divers. 2022; 27(3):1163-1184.

PMID: 35879631 DOI: 10.1007/s11030-022-10480-y.

Proteomic Characterization and Target Identification Against Streptococcus mutans Under Bacitracin Stress Conditions Using LC-MS and Subtractive Proteomics.

Zaidi S, Bhardwaj T, Somvanshi P, Khan A Protein J. 2022; 41(1):166-178.

PMID: 34989956 PMC: 8733428. DOI: 10.1007/s10930-021-10038-1.

Comparative proteomic analysis to annotate the structural and functional association of the hypothetical proteins of S. maltophilia k279a and predict potential T and B cell targets for vaccination.

Ezaj M, Haque M, Syed S, Khan M, Ahmed K, Khatun M PLoS One. 2021; 16(5):e0252295.

PMID: 34043709 PMC: 8159010. DOI: 10.1371/journal.pone.0252295.

Computational Identification of Essential Enzymes as Potential Drug Targets in Pathogenesis Using Metabolic Pathway Analysis and Epitope Mapping.

Narad P, Himanshu , Bansal H J Microbiol Biotechnol. 2020; 31(4):621-629.

PMID: 33323673 PMC: 9723279. DOI: 10.4014/jmb.2007.07006.

References

Ikemura T . Codon usage and tRNA content in unicellular and multicellular organisms. Mol Biol Evol. 1985; 2(1):13-34. DOI: 10.1093/oxfordjournals.molbev.a040335. View

Sakharkar K, Sakharkar M, Chow V . A novel genomics approach for the identification of drug targets in pathogens, with special reference to Pseudomonas aeruginosa. In Silico Biol. 2005; 4(3):355-60. View

Rathi B, Sarangi A, Trivedi N . Genome subtraction for novel target definition in Salmonella typhi. Bioinformation. 2010; 4(4):143-50. PMC: 2825597. DOI: 10.6026/97320630004143. View

Grosjean H, Fiers W . Preferential codon usage in prokaryotic genes: the optimal codon-anticodon interaction energy and the selective codon usage in efficiently expressed genes. Gene. 1982; 18(3):199-209. DOI: 10.1016/0378-1119(82)90157-3. View

Sharp P, Li W . The codon Adaptation Index--a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 1987; 15(3):1281-95. PMC: 340524. DOI: 10.1093/nar/15.3.1281. View

Lynn D, Singer G, Hickey D . Synonymous codon usage is subject to selection in thermophilic bacteria. Nucleic Acids Res. 2002; 30(19):4272-7. PMC: 140546. DOI: 10.1093/nar/gkf546. View

Ermolaeva M . Synonymous codon usage in bacteria. Curr Issues Mol Biol. 2001; 3(4):91-7. View

Kloosterman T, van der Kooi-Pol M, Bijlsma J, Kuipers O . The novel transcriptional regulator SczA mediates protection against Zn2+ stress by activation of the Zn2+-resistance gene czcD in Streptococcus pneumoniae. Mol Microbiol. 2007; 65(4):1049-63. DOI: 10.1111/j.1365-2958.2007.05849.x. View

Dutta A, Singh S, Ghosh P, Mukherjee R, Mitter S, Bandyopadhyay D . In silico identification of potential therapeutic targets in the human pathogen Helicobacter pylori. In Silico Biol. 2006; 6(1-2):43-7. View

10.

Mushegian A, Koonin E . A minimal gene set for cellular life derived by comparison of complete bacterial genomes. Proc Natl Acad Sci U S A. 1996; 93(19):10268-73. PMC: 38373. DOI: 10.1073/pnas.93.19.10268. View

11.

Read R, Rutman A, Jeffery P, Lund V, Brain A, Moxon E . Interaction of capsulate Haemophilus influenzae with human airway mucosa in vitro. Infect Immun. 1992; 60(8):3244-52. PMC: 257308. DOI: 10.1128/iai.60.8.3244-3252.1992. View

12.

Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M . KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 1998; 27(1):29-34. PMC: 148090. DOI: 10.1093/nar/27.1.29. View

13.

Anishetty S, Pulimi M, Pennathur G . Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis. Comput Biol Chem. 2005; 29(5):368-78. DOI: 10.1016/j.compbiolchem.2005.07.001. View

14.

Fleischmann R, Adams M, White O, Clayton R, Kirkness E, Kerlavage A . Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995; 269(5223):496-512. DOI: 10.1126/science.7542800. View

15.

Chong C, Lim B, Nathan S, Mohamed R . In silico analysis of Burkholderia pseudomallei genome sequence for potential drug targets. In Silico Biol. 2006; 6(4):341-6. View

16.

Huynen M, Dandekar T, Bork P . Differential genome analysis applied to the species-specific features of Helicobacter pylori. FEBS Lett. 1998; 426(1):1-5. DOI: 10.1016/s0014-5793(98)00276-2. View

17.

Bolotin A, Quinquis B, Renault P, Sorokin A, Ehrlich S, Kulakauskas S . Complete sequence and comparative genome analysis of the dairy bacterium Streptococcus thermophilus. Nat Biotechnol. 2004; 22(12):1554-8. PMC: 7416660. DOI: 10.1038/nbt1034. View

18.

Hols P, Hancy F, Fontaine L, Grossiord B, Prozzi D, Leblond-Bourget N . New insights in the molecular biology and physiology of Streptococcus thermophilus revealed by comparative genomics. FEMS Microbiol Rev. 2005; 29(3):435-63. DOI: 10.1016/j.femsre.2005.04.008. View

19.

Akashi H . Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy. Genetics. 1994; 136(3):927-35. PMC: 1205897. DOI: 10.1093/genetics/136.3.927. View

20.

Hong S, Kim J, Lee S, In Y, Choi S, Rih J . The genome sequence of the capnophilic rumen bacterium Mannheimia succiniciproducens. Nat Biotechnol. 2004; 22(10):1275-81. DOI: 10.1038/nbt1010. View