In silico identification of common putative drug targets in Leptospira interrogans
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ORIGINAL ARTICLE
In silico identification of common putative drug targets in Leptospira interrogans U. Amineni & D. Pradhan & H. Marisetty
Received: 6 December 2009 / Accepted: 22 April 2010 / Published online: 14 May 2010 # Springer-Verlag 2010
Abstract Infectious diseases are the leading causes of death worldwide. Hence, there is a need to develop new antimicrobial agents. Traditional method of drug discovery is time consuming and yields a few drug targets with little intracellular information for guiding target selection. Thus, focus in drug development has been shifted to computational comparative genomics for identifying novel drug targets. Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. Availability of L. interrogans serovars and human genome sequences facilitated to search for novel drug targets using bioinformatics tools. The genome sequence of L. interrogans serovar Copenhageni has 5,124 genes while that of serovar Lai has 4,727 genes. Through subtractive genomic approach 218 genes in serovar Copenhageni and 158 genes in serovar Lai have been identified as putative drug targets. Comparative genomic approach had revealed that 88 drug targets were common to both the serovars. Pathway analysis using the Kyoto Encyclopaedia of Genes and Genomes revealed that 66 targets are enzymes and 22 are non-enzymes. Sixty two common drug targets were predicted to be localized in cytoplasm and 16 were surface proteins. The identified potential drug targets form a platform for further investigation in discovery of novel therapeutic compounds against Leptospira.
U. Amineni (*) : D. Pradhan SVIMS Bioinformatics Centre, SVIMS University, Tirupati, AP, India 517 507 e-mail: [email protected] H. Marisetty Agricultural Research Station, Perumallapalle, Tirupati 517507 AP, India
Keywords Leptospirosis . Subtractive genomics approach . Novel drug targets . KEGG
Introduction The widespread emergence of bacterial resistance to existing antibiotics is a global health threat and has emphasized the need to develop new antibacterial agents directed towards novel targets [1]. Leptospirosis is a globally widespread infectious zoonosis with more than 500,000 severe cases annually in the world [2]. Human leptospirosis is caused mainly by spirochete pathogen Leptospira interrogans [3]. People exposed to recreational activities, farming, and post-flood conditions are at major risk of getting infected through contaminated water, rodents, or pet animals [4, 5]. High prevalence of leptospiral antibodies was observed in rural areas with sanitation workers and sugarcane workers being the most frequent victims [6, 7]. Leptospirosis occurs as either anicteric leptospirosis syndromes in 85-90% of cases or icteric leptospirosis in 5-10% of cases. In anicteric leptospirosis, there are two stages, viz., septicemia stage and the immune stage. Symptoms of infection include fever, chills, headache, and severe myalgia. In 5-15% cases, multiple organ damage is reported and the mortality rate has been shown to b
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