In silico identification of putative drug targets in pseudomonas aeruginosa through metabolic pathway analysis

Deepak Perumal, Chu Sing Lim, Meena K. Sakharkar

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

9 Scopus citations

Abstract

Comparative genomic analysis between pathogens and the host Homo sapiens has led to identification of novel drug targets. Microbial drug target identification and validation has been the latest trend in pharmacoinformatics. In order to identify a suitable drug target for the pathogen Pseudomonas aeruginosa an in silico comparative analysis of the metabolic pathways between the pathogen and the host Homo sapiens was performed. Detection of bacterial genes that are non-homologous to human genes, and are essential for the survival of the pathogen represents a promising means of identifying novel drug targets. Metabolic pathways for the pathogen and H. sapiens were obtained from the metabolic pathway database KEGG and were compared to identify unique pathways present only in the pathogen and absent in the host. We identified 361 enzymes from both unique and common pathways between the pathogen and the host of which 50 belong to the 12 unique pathways. Enzymes from both genomes were subject to a BLASTp search and sequences homologous to human were removed as non essential. P.aeruginosa targets without human homologs were identified when the e-value threshold was set as 10-2. Of the 214 targets that had no hits only 30 targets belong to unique pathways. These 30 targets were then compared with the list of candidate essential genes identified by mutagenesis. Only 8 targets matched with the essential genes list and these were considered as potential drug targets. We have built homology model for the four target genes lpxC, kdsA, kdsB and waaG using MODELLER software. This approach enables rapid potential drug target identification, thereby greatly facilitating the search for new antibiotics.

Original languageEnglish
Title of host publicationPattern Recognition in Bioinformatics - Second IAPR International Workshop, PRIB 2007, Proceedings
PublisherSpringer Verlag
Pages323-336
Number of pages14
ISBN (Print)9783540752851
DOIs
StatePublished - 2007
Externally publishedYes
Event2nd IAPR International Workshop on Pattern Recognition in Bioinformatics, PRIB 2007 - Singapore, Singapore
Duration: 1 Oct 20072 Oct 2007

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume4774 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference2nd IAPR International Workshop on Pattern Recognition in Bioinformatics, PRIB 2007
Country/TerritorySingapore
CitySingapore
Period1/10/072/10/07

Keywords

  • Comparative microbial genomics
  • Homo sapiens
  • Homology
  • KEGG
  • KdsA
  • KdsB
  • LpxC
  • MODELLER
  • Potential drug targets
  • Pseudomonas aeruginosa
  • WaaG

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