Comparative assessment of the therapeutic drug targets of C. botulinum ATCC 3502 and C. difficile str. 630 using in silico subtractive proteomics approach.
Tulika BhardwajShafiul HaquePallavi SomvanshiPublished in: Journal of cellular biochemistry (2019)
Growing antimicrobial resistance of the pathogens against multiple drugs posed a serious threat to the human health worldwide. This fueled the need of identifying the novel therapeutic targets that can be used for developing new class of the drugs. Recently, there is a substantial rise in the rate of Clostridium infections as well as in the emergence of virulent and antibiotic resistant strains. Hence, there is an urgent need for the identification of potential therapeutic targets and the development of new drugs for the treatment and prevention of Clostridium infections. In the present study, a combinatorial approach involving systems biology and comparative genomics strategy was tested against Clostridium botulinum ATCC 3502 and Clostridium difficile str. 630 pathogens, to render potential therapeutic target at qualitative and quantitative level. This resulted in the identification of five common (present in both the pathogens, 34 in C. botulinum ATCC 3502 and 42 in C. difficile str. 630) drug targets followed by virtual screening-based identification of potential inhibitors employing molecular docking and molecular dynamics simulations. The identified targets will provide a solid platform for the designing of novel wide-spectrum lead compounds capable of inhibiting their catalytic activities against multidrug-resistant Clostridium in the near future.
Keyphrases
- molecular docking
- antimicrobial resistance
- human health
- molecular dynamics simulations
- clostridium difficile
- gram negative
- risk assessment
- multidrug resistant
- climate change
- drug induced
- bioinformatics analysis
- escherichia coli
- drug resistant
- acinetobacter baumannii
- signaling pathway
- high throughput
- high resolution
- single cell
- klebsiella pneumoniae