J Vet Sci.  2018 Mar;19(2):188-199. 10.4142/jvs.2018.19.2.188.

In silico analysis of putative drug and vaccine targets of the metabolic pathways of Actinobacillus pleuropneumoniae using a subtractive/comparative genomics approach

• Birhanu BT
• Lee SJ
• Park NH
• Song JB
• Park SC

• KMID: 2407618
• DOI: http://doi.org/10.4142/jvs.2018.19.2.188

Abstract

Actinobacillus pleuropneumoniae is a Gram-negative bacterium that resides in the respiratory tract of pigs and causes porcine respiratory disease complex, which leads to significant losses in the pig industry worldwide. The incidence of drug resistance in this bacterium is increasing; thus, identifying new protein/gene targets for drug and vaccine development is critical. In this study, we used an in silico approach, utilizing several databases including the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database of Essential Genes (DEG), DrugBank, and Swiss-Prot to identify non-homologous essential genes and prioritize these proteins for their druggability. The results showed 20 metabolic pathways that were unique and contained 273 non-homologous proteins, of which 122 were essential. Of the 122 essential proteins, there were 95 cytoplasmic proteins and 11 transmembrane proteins, which are potentially suitable for drug and vaccine targets, respectively. Among these, 25 had at least one hit in DrugBank, and three had similarity to metabolic proteins from Mycoplasma hyopneumoniae, another pathogen causing porcine respiratory disease complex; thus, they could serve as common therapeutic targets. In conclusion, we identified glyoxylate and dicarboxylate pathways as potential targets for antimicrobial therapy and tetra-acyldisaccharide 4"²-kinase and 3-deoxy-D-manno-octulosonic-acid transferase as vaccine candidates against A. pleuropneumoniae.

Keyword

Actinobacillus pleuropneumoniae; drug target; in silico; metabolic networks and pathways; vaccine target

MeSH Terms

Actinobacillus pleuropneumoniae*
Actinobacillus*
Computer Simulation*
Cytoplasm
Databases, Protein
Drug Resistance
Genes, Essential
Genome
Genomics*
Incidence
Metabolic Networks and Pathways*
Mycoplasma hyopneumoniae
Pleuropneumonia
Respiratory System
Swine
Transferases
Transferases

Figure

• 

  Fig. 1 Schematic of the in silico method used. Each protein was checked for homology in the respective databases. NCBI, National Center for Biotechnology Information; KEGG, Kyoto Encyclopedia of Genes and Genomes; DEG, Database of Essential Genes; PDB, Protein Data Bank; 3D, three-dimensional.

• 

  Fig. 2 Number of Actinobacillus pleuropneumoniae genes with essential gene hits in the Database of Essential Genes (DEG). The essential genes of A. pleuropneumoniae were identified by comparison to those of all 36 bacteria in the DEG.

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