Genome-Based Drug Target Identification in Human Pathogen Streptococcus gallolyticus

Abstract

Streptococcus gallolysticus (Sg) is an opportunistic Gram-positive, non-motile bacterium, which causes infective endocarditis, an inflammation of the inner lining of the heart. As Sg has acquired resistance with the available antibiotics, therefore, there is a dire need to find new therapeutic targets and potent drugs to prevent and treat this disease. In the current study, an in silico approach is utilized to link genomic data of Sg species with its proteome to identify putative therapeutic targets. A total of 1,138 core proteins have been identified using pan genomic approach. Further, using subtractive proteomic analysis, a set of 18 proteins, essential for bacteria and non-homologous to host (human), is identified. Out of these 18 proteins, 12 cytoplasmic proteins were selected as potential drug targets. These selected proteins were subjected to molecular docking against drug-like compounds retrieved from ZINC database. Furthermore, the top docked compounds with lower binding energy were identified. In this work, we have identified novel drug and vaccine targets against Sg, of which some have already been reported and validated in other species. Owing to the experimental validation, we believe our methodology and result are significant contribution for drug/vaccine target identification against Sg-caused infective endocarditis.

In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against Streptococcus pyogenes

“…A total of 10 S. pyogenes essential proteins were involved in these 6 pathways. The results of pathogen-specific pathway identification are consistent with those reported by Goyal et al, Amineni et al, and Shahid et al for A. baumannii, L. interrogans, and S. saprophyticus, respectively [13,55]. Eight out of the ten proteins were found to be involved in H. sapiens and S. pyogenes pathways.…”

Comparative analysis of 31 Streptococcus gallolyticus strains uncovers their potential risks from the perspectives of virulence factors and antibiotic resistance genes

“…These results suggested that with the emergence of new S. gallolyticus strains, the size of the pangenome of S. gallolyticus tended to increase gradually, while the size of the core genome decreased gradually. In particular, our results showed that the number of genes/proteins a liated with the core genome of S. gallolyticus was smaller than that of a previous study [15]. These results suggested that with the increase of the genome of S. gallolyticus, the size of the pan-genome of S. gallolyticus would lead to the expansion and the increase of genomic diversity.…”

“…To identify potential therapeutic targets of S. gallolyticus, 12 cytoplasmic proteins were selected as putative drug targets using both a pan-genome approach and subtractive proteomic analysis, which linked genomic data from the S. gallolyticus species to its proteome [15]. However, the speci c traits of the pan-genome of S. gallolyticus were still not completely elucidated.…”

Potential Therapeutic Candidates against Chlamydia pneumonia Discovered and Developed In Silico Using Core Proteomics and Molecular Docking and Simulation-Based Approaches

“…The best way to uncover novel medicines may be to target non-homologous sequences. Researchers found that 681 pathogen-specific metabolic pathways exist using the KEGG database, while pathogens and hosts share 14 pathways [ 18 , 50 ]. Only three of these fourteen proteins (30S ribosomal protein S4, 4-hydroxybenzoate decarboxylase subunit C, and oligopeptide binding protein) were identified as pathogen-specific.…”