Abstract
Leprosy is an infectious disease caused by Mycobacterium leprae. M. leprae has undergone a major reductive evolution leaving a minimal set of functional genes for survival. It remains non-cultivable. As M. leprae develops resistance against most of the drugs, novel drug targets are required in order to design new drugs. As most of the essential genes mediate several biosynthetic and metabolic pathways, the pathway predictions can predict essential genes. We used comparative genome analysis of metabolic enzymes in M. leprae and H. sapiens using KEGG pathway database and identified 179 non-homologues enzymes. On further comparison of these 179 non-homologous enzymes to the list of minimal set of 48 essential genes required for cell-wall biosynthesis of M. leprae reveals eight common enzymes. Interestingly, six of these eight common enzymes map to that of peptidoglycan biosynthesis and they all belong to Mur enzymes. The machinery for peptidoglycan biosynthesis is a rich source of crucial targets for antibacterial chemotherapy and thus targeting these enzymes is a step towards facilitating the search for new antibiotics.
Highlights
The availability of the complete genome sequences of several pathogenic bacteria and the completion of the human genome project has revolutionized the field of drug-discovery against threatening human pathogens [1]
The other half contains pseudo genes and non-coding sequences. These findings indicate that M. leprae has undergone a major reductive evolution leaving a minimal set of functional genes for survival [4]
We present a computational approach to identify the genes essential to M. leprae using comparative pathway analysis followed by mapping of non-homologues genes with list of minimal set of essential genes required for cell-wall biosynthesis of M. leprae
Summary
The availability of the complete genome sequences of several pathogenic bacteria and the completion of the human genome project has revolutionized the field of drug-discovery against threatening human pathogens [1]. A target should provide adequate selectivity yielding a drug which is specific or highly selective against the pathogen with respect to the human host. Computer analysis demonstrated that only half of the sequence contains protein-coding genes. The other half contains pseudo genes and non-coding sequences. These findings indicate that M. leprae has undergone a major reductive evolution leaving a minimal set of functional genes for survival [4]. Resistant strains of M. leprae appeared due to mutations in the macrolide target, the ribosome [7]. We present a computational approach to identify the genes essential to M. leprae using comparative pathway analysis followed by mapping of non-homologues genes with list of minimal set of essential genes required for cell-wall biosynthesis of M. leprae. Our approach successfully identified a unique group of common enzymes as promising protein targets for new antibiotic development and further characterization in the laboratory
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