Genome-wide screening and in silico gene knockout to predict potential candidates for drug designing against Candida albicans.

Genome-wide screening and in silico gene knockout to predict potential candidates for drug designing against Candida albicans. Infect Genet Evol. 2020 Jan 16;:104196 Authors: Verma R, Pradhan D, Maseet M, Singh H, Jain AK, Khan LA Abstract C. albicans infections are increasingly becoming a threat to public health with emergence of drug resistant strains. It emphasizes the need to look for alternate drug targets through genome-wide screening. In the present study, whole proteome of C. albicans SC5314 was analyzed in single click target mining workflow of TiDv2. A protein-protein interaction network (PPI) for the resulting putative targets was generated based on String database. Ninety four proteins with higher connectivity (degree ≥10) in the network are noted as hub genes. Among them, 24 are observed to be known targets while 70 are novel ones. Further, chokepoint analysis revealed FAS2, FOL1 and ERG5 as chokepoint enzymes in their respective pathways. Subsequently, the chokepoints were selected as prior interest for in silico gene knockout via MATLAB and COBRA Toolbox. In silico gene knockout pointed that FAS2 inhibition reduced the growth rate of pathogen from 0.2879 mmol.gDW-1.h-1 to zero. Furthermore, enzyme inhibition assay of FAS2 with cerulenin strengthen the computational outcome with MIC 1.25 μg/ml. Hence, the study establishes FAS2 as a promising target to design therapeutics against C. albicans. PMID: 319549...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research