title: A novel comparative genomics analysis for common drug and vaccine targets in Corynebacterium pseudotuberculosis and other CMN group of human pathogens.
abstract: Caseous lymphadenitis is a chronic goat and sheep disease caused by Corynebacterium pseudotuberculosis (Cp) that accounts for a huge economic loss worldwide. Proper vaccination or medication is not available because of the lack of understanding of molecular biology of the pathogen. In a recent approach, four Cp (CpFrc41, Cp1002, CpC231, and CpI-19) genomes were sequenced to elucidate the molecular pathology of the bacteria. In this study, using these four genome sequences along with other eight genomes (total 12 genomes) and a novel subtractive genomics approach (first time ever applied to a veterinary pathogen), we identified potential conserved common drug and vaccine targets of these four Cp strains along with other Corybacterium, Mycobacterium and Nocardia (CMN) group of human pathogens (Corynebacterium diphtheriae and Mycobacterium tuberculosis) considering goat, sheep, bovine, horse, and human as the most affected hosts. The minimal genome of Cp1002 was found to consist of 724 genes, and 20 conserved common targets (to all Cp strains as well as CMN group of pathogens) from various metabolic pathways (13 from host-pathogen common and seven from pathogen's unique pathways) are potential targets irrespective of all hosts considered. ubiA from host-pathogen common pathway and an ABC-like transporter from unique pathways may serve dual (drug and vaccine) targets. Two Corynebacterium-specific (mscL and resB) and one broad-spectrum (rpmB) novel targets were also identified. Strain-specific targets are also discussed. Six important targets were subjected to virtual screening, and one compound was found to be potent enough to render two targets (cdc and nrdL). We are currently validating all identified targets and lead compounds.
authors: Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India. dr.barh@gmail.com
authors: Debmalya
authors: D
authors: Barh
authors: Neha
authors: N
authors: Jain
authors: Sandeep
authors: S
authors: Tiwari
authors: Bibhu Prasad
authors: BP
authors: Parida
authors: Vivian
authors: V
authors: D'Afonseca
authors: Liwei
authors: L
authors: Li
authors: Amjad
authors: A
authors: Ali
authors: Anderson Rodrigues
authors: AR
authors: Santos
authors: Luís Carlos
authors: LC
authors: Guimarães
authors: Siomar
authors: S
authors: de Castro Soares
authors: Anderson
authors: A
authors: Miyoshi
authors: Atanu
authors: A
authors: Bhattacharjee
authors: Amarendra Narayan
authors: AN
authors: Misra
authors: Artur
authors: A
authors: Silva
authors: Anil
authors: A
authors: Kumar
authors: Vasco
authors: V
authors: Azevedo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001428:Bacterial Vaccines / Q000276:immunology*; D055028:Comparative Genomic Hybridization; D016925:Corynebacterium pseudotuberculosis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D015195:Drug Design; D016680:Genome, Bacterial; D006801:Humans; D009161:Mycobacterium / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009615:Nocardia / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines