4 - Central Institute of Brackishwater Aquaculture

National Workshop-cum-Tra~nlng on Blolnformatiu and Infomatlon Management in Aquacultum
SUBTRACTIVE GENOMIC APPROACH TO IDENTIFY
POTENTIAL DRUG TARGETS AND ACTIVE SITES I N
CHLAMYDOPHILA PNEUMONIAE
S C Patnaik, E H K Reddy, Gyana R Satpathy'
Abstract
Whole genome sequences of the human pathogen Chlamydophila pneumoniae
and four other strains of same species were analyzed to identify common drug
targets. A substractive genomic approach is applied to identify Holliday junction
DNA helicase RuvB as the common non-human homologous gene among these
four strains. A three-dimensional model of the Holliday junction DNA helicase
RuvB protein was generated with homology modelling. The protein is analysed
for identification of suitable target sites.
Keywords: Chlamydophila pneumoniae, BLAST, MSA, homologous,
modeling, active site
homology
1. Introduction
Chlamydophila pneumoniae is a widespread obligate intracellular gram negative
bacterium that causes upper and lower respiratory infections worldwide
[Grayston et al., 19901. In addition to acute infections, several chronic
inflammatory diseases have been associated with C, pneumoniae infection.
Increasing evidence implicates that a persistent lung infection caused by C.
pneumoniae may contribute to the initiation, exacerbation and promotion of
asthma symptoms [Hahn, 1999; Cazzola et al., 20041.
Identification of the target molecule inside various metabolic pathways is the first
step when designing drugs against a pathogen. The vastness of the pathogen
genomes has made this work more difficult involving considarable sum of labor
and time. As microbial populations have rapid growth rates, evolution of
resistance can occur in relatively short time frames. Moreover, resistance genes
can be dispersed rapidly by genetic exchange systems among diverse bacterial
specles. It is therefore essential to develop rapid processes to identify novel
antibiotics. Genes that are conserved in different organism often turn out to be
essential. These essential genes should not have any well-conserved homolog in
the human host. Inactivation of essential genes by any drug should result in the
lethal phenotype in the pathogen [Judson and Mekalanos, 20001.
Large amount of sequence data is generated from various microbial genome
sequencing projects around the world. These datasets create a major challenge
in the post-genomic era. The strategies for drug design and development are
increasingly shifting from the genetic approach to the genomic approach
[Galperin and Koonin, 19991. Subtractive genomics has been successfully used
by authors to locate novel drug targets in Pseudomonas aeruginosa, Helicobactor
'Correspondence: Gyana Ranjan Satpathy, Coordinator, Bioinformatics Centre, National
Institute of Technology, Rourkela-769008, India: Email: gyanasatpathy@gmaiI.com