Genomics Inform.  2016 Dec;14(4):255-264. 10.5808/GI.2016.14.4.255.

Mining the Proteome of Fusobacterium nucleatum subsp. nucleatum ATCC 25586 for Potential Therapeutics Discovery: An In Silico Approach

• Habib AM
• Islam MS
• Sohel M
• Mazumder M
• Sikder MO
• Shahik SM

• KMID: 2366444
• DOI: http://doi.org/10.5808/GI.2016.14.4.255

Abstract

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

Keyword

colon neoplasms; drug delivery systems; Fusobacterium nucleatum; homolog; ligands

MeSH Terms

Anti-Bacterial Agents
Bacteria
Binding Sites
Colonic Neoplasms
Colorectal Neoplasms
Computer Simulation*
Drug Delivery Systems
Drug Discovery
Fusobacterium nucleatum*
Fusobacterium*
Genes, Essential
Genome
Genome, Human
Genomics
Humans
Ligands
Mass Screening
Mining*
Proteome*
Anti-Bacterial Agents
Ligands
Proteome