A Novel Comparative Genomics Analysis for Common Drug and Vaccine Targets inCorynebacterium pseudotuberculosisand 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.

Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in Vibrio cholerae Targeted by Piper betel Derived Compounds

“…We applied the classical reverse vaccinology strategy [10] and a modified method of subtractive proteomics [15], [16] to identify candidate drug vaccine targets in V. cholerae strain O395 and other Vibrio serotypes. In brief, the Vibrio cholera O395 proteome, which consists of 3875 proteins, was screened using CELLO [17], PSLpred [18], PSORTb [19], SOSUI-GramN [20], and SurfG + [21] to identify the exomembrane and secreted proteins.…”

“…In brief, the Vibrio cholera O395 proteome, which consists of 3875 proteins, was screened using CELLO [17], PSLpred [18], PSORTb [19], SOSUI-GramN [20], and SurfG + [21] to identify the exomembrane and secreted proteins. Thereafter, the essential, non-human homolog Vibrio proteins (putative targets) from the pool of exoproteome and secretome were identified using the Database of Essential Genes (DEG) [22] and NCBI BLASTp [23], as described by Barh et al, 2011 [15]. Selected non-human homolog essential Vibrio proteins were then checked for their pathway involvement, and the best targets were selected based on the involvements of these targets in the unique essential bacterial metabolic pathways and another twelve criteria as described by Barh et al, 2011 [15] for target selection.…”

An In Silico Identification of Common Putative Vaccine Candidates against Treponema pallidum: A Reverse Vaccinology and Subtractive Genomics Based Approach

“…Approaches, such as comparative and subtractive genomics and differential genome analyses [16], are being widely utilized for target identification in several human pathogens, including Mycobacterium tuberculosis [17], Helicobacter pylori [18], Burkholderia pseudomallei [19], Pseudomonas aeruginosa [20], Salmonella typhi [21], and Neisseria gonorrhoeae [22]. Generally, the principle behind these approaches is the identification of gene/protein targets that are essential for the survival of the pathogen but are not homologous to genes/proteins of the host [23]. Nevertheless, the identified targets may have a certain degree of homology with the host protein and are essential for the survival of the pathogen; hence, they can also be selected for structure-based selective inhibitor development as an additional molecular target.…”

Progression of ‘Omics’ Methodologies for Understanding the Pathogenicity of Corynebacterium Pseudotuberculosis: The Brazilian Experience

“…The sequencing of several strains of C. pseudotuberculosis is paving the way for further studies. In 2011, Barh and colleagues compared four genomes of C. pseudotuberculosis (strains FRC41, 1002, C231 and I19) with eight other sequenced genomes of pathogens belonging to a group that includes genera such Corynebacterium, Mycobacterium, Nocardia and Rhodococcus , which are commonly found in humans, goats, sheep, cattle and horses [5]. As a result of this comparative genomic analysis, potential molecular targets were identified for the production of drugs and vaccines.…”