scholarly journals Integrated bioinformatics based subtractive genomics approach to decipher the therapeutic function of hypothetical proteins from Salmonella typhi XDR H-58 strain

2022 ◽  
Author(s):  
Kanwal Khan ◽  
Reaz Uddin
Keyword(s):  
Salmonella Typhi ◽  
Hypothetical Proteins ◽  
Subtractive Genomics ◽  
Therapeutic Function ◽  
Subtractive Genomics Approach

scholarly journals Identification of potential candidates for drug designing against Klebsiella Pneumoniae among hypothetical proteins of DNA Adenine Methyltransferase through subtractive genomics approach

2020 ◽  
Author(s):  
Umairah Natasya Mohd Omeershffudin ◽  
Suresh Kumar
Keyword(s):  
Klebsiella Pneumoniae ◽  
Drug Target ◽  
Bacterial Pathogens ◽  
Hypothetical Proteins ◽  
Homology Analysis ◽  
Subtractive Genomics ◽  
Natural Inhibitor ◽  
Subtractive Genomics Approach ◽  
Dna Adenine Methyltransferase ◽  
Selection Of

ABSTRACTKlebsiella Pneumoniae is a gram-negative bacterium that is known for causing infection in nosocomial settings. As reported by WHO, this bacterial pathogen is classified as an urgent threat our most concern is that these bacterial pathogens acquired genetic traits that make them resistant towards antibiotics. The last class of antibiotics; carbapenems are not able to combat these bacterial pathogens allowing them to clonally expand their antibiotic-resistant strain. Most antibiotics target the essential pathways of the bacteria cell however these targets are no longer susceptible to the antibiotic. Hence in our study, we focus on Klebsiella Pneumoniae bacterial strains that contain DNA Adenine Methyltransferase domain which suggests a new potential site for a drug target. DNA methylation is seen to regulate the attenuation of bacterial virulence. In this study, all hypothetical proteins of Klebsiella Pneumoniae containing N6 DNA Adenine Methyltransferase domain were analysed for a potential drug target. About 32 hypothetical proteins were retrieved from Uniprot. 19 proteins were selected through a step-wise subtractive genomics approach like a selection of non-homologus proteins against the human host, selection of bacterial proteins contains an essential gene, broad-spectrum analysis, druggability analysis, Non-homology analysis against gut microbiota. Through drug target prioritization like sub-cellular analysis, drug property analysis, anti-target non-homology analysis, virulence factor analysis and protein-protein interaction analysis one drug target protein (Uniprot ID: A0A2U0NNR3) was prioritized. Identified drug target docked with potential inhibitors like are mahanine (PubChem ID: 375151), curcumin (PubChem ID: 969516), EGCG (PubChem ID: 65064), nanaomycin A (PubChem ID: 40586), parthenolide (PubChem ID: 7251185), quercetin (PubChem ID: 5280343) and trimethylaurintricarboxylic acid. Based on the moelcular docking analysis, mahanine has the highest binding affinity. In order to identify novel natural inhibitor based on mahanine fingerprint search is performed against NPASS (Natural Product Activity and Species Source databases) and Koenimbine was identified as a novel natural inhibitor based on virtual screening.

scholarly journals Identification of potential drug targets and vaccine candidates in Clostridium botulinum using subtractive genomics approach

2019 ◽  
Vol 15 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Rati Sudha ◽  
◽  
Amit Katiyar ◽  
Poonam Katiyar ◽  
Harpreet Singh ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Drug Targets ◽  
Potential Drug ◽  
Vaccine Candidates ◽  
Subtractive Genomics ◽  
Subtractive Genomics Approach ◽  
Potential Drug Targets

scholarly journals Identification of a Novel Therapeutic Target against XDR Salmonella Typhi H58 Using Genomics Driven Approach Followed Up by Natural Products Virtual Screening

2021 ◽  
Vol 9 (12) ◽  
pp. 2512
Author(s):  
Khurshid Jalal ◽  
Kanwal Khan ◽  
Muhammad Hassam ◽  
Muhammad Naseer Abbas ◽  
Reaz Uddin ◽  
...  
Keyword(s):  
Typhoid Fever ◽  
Drug Targets ◽  
Salmonella Typhi ◽  
Drug Resistant ◽  
Acid Biosynthesis ◽  
New Drug ◽  
Subtractive Genomics ◽  
Colanic Acid ◽  
Novel Drug ◽  
Potential Drug Targets

Typhoid fever is caused by a pathogenic, rod-shaped, flagellated, and Gram-negative bacterium known as Salmonella Typhi. It features a polysaccharide capsule that acts as a virulence factor and deceives the host immune system by protecting phagocytosis. Typhoid fever remains a major health concern in low and middle-income countries, with an estimated death rate of ~200,000 per annum. However, the situation is exacerbated by the emergence of the extensively drug-resistant (XDR) strain designated as H58 of S. Typhi. The emergence of the XDR strain is alarming, and it poses serious threats to public health due to the failure of the current therapeutic regimen. A relatively newer computational method called subtractive genomics analyses has been widely applied to discover novel and new drug targets against pathogens, particularly drug-resistant ones. The method involves the gradual reduction of the complete proteome of the pathogen, leading to few potential and novel drug targets. Thus, in the current study, a subtractive genomics approach was applied against the Salmonella XDR strain to identify potential drug targets. The current study predicted four prioritized proteins (i.e., Colanic acid biosynthesis acetyltransferase wcaB, Shikimate dehydrogenase aroE, multidrug efflux RND transporter permease subunit MdtC, and pantothenate synthetase panC) as potential drug targets. Though few of the prioritized proteins are treated in the literature as the established drug targets against other pathogenic bacteria, these drug targets are identified here for the first time against S. Typhi (i.e., S. Typhi XDR). The current study aimed at drawing attention to new drug targets against S. Typhi that remain largely unexplored. One of the prioritized drug targets, i.e., Colanic acid biosynthesis acetyltransferase, was predicted as a unique, new drug target against S. Typhi XDR. Therefore, the Colanic acid was further explored using structure-based techniques. Additionally, ~1000 natural compounds were docked with Colanic acid biosynthesis acetyltransferase, resulting in the prediction of seven compounds as potential lead candidates against the S. Typhi XDR strain. The ADMET properties and binding energies via the docking program of these seven compounds characterized them as novel drug candidates. They may potentially be used for the development of future drugs in the treatment of Typhoid fever.

scholarly journals Subtractive genomics approach towards the identification of novel therapeutic targets against human Bartonella bacilliformis

2020 ◽  
Vol 20 ◽  
pp. 100385
Author(s):  
Md. Tahsin Khan ◽  
Araf Mahmud ◽  
Asif Iqbal ◽  
Syeda Farjana Hoque ◽  
Mahmudul Hasan
Keyword(s):  
Therapeutic Targets ◽  
Bartonella Bacilliformis ◽  
Subtractive Genomics ◽  
Subtractive Genomics Approach ◽  
Novel Therapeutic

Potential Drug Targets Identification against Clostridioides difficile (CD) and Characterization of Indispensable Proteins by a Subtractive Genomics Approach Followed by Virtual Screening

2021 ◽  
Vol 18 ◽  
Author(s):  
Reaz Uddin ◽  
Alina Arif
Keyword(s):  
Drug Targets ◽  
Drug Resistant ◽  
Potential Drug ◽  
Drug Candidates ◽  
Subtractive Genomics ◽  
Clostridioides Difficile ◽  
Subtractive Genomics Approach ◽  
Novel Drug ◽  
Potential Drug Targets ◽  
Novel Drug Targets

Background: Clostridioides difficile (CD) is a multi-drug resistant, enteric pathogenic bacterium. The CD associated infections are the leading cause of nosocomial diarrhea that can further lead to pseudomembranous colitis up to a toxic mega-colon or sepsis with greater mortality and morbidity risks. The CD infection possess higher rates of recurrence due to its greater resistance against antibiotics. Considering its higher rates of recurrence, it has become a major burden on the healthcare facilities. Therefore, there is a dire need to identify novel drug targets to combat with the antibiotic resistance of Clostridioides difficile. Objective: To identify and propose new and novel drug targets against the Clostridioides difficile. Methods: In the current study, a computational subtractive genomics approach was applied to obtain a set of potential drug targets that exists in the multi-drug resistant strain of Clostridioides difficile. Here, the uncharacterized proteins were studied as potential drug targets. The methodology involved several bioinformatics databases and tools. The druggable proteins sequences were retrieved based on non-homology with host proteome and essentiality for the survival of the pathogen. The uncharacterized proteins were functionally characterized using different computational tools and sub-cellular localization was also predicted. The metabolic pathways were analyzed using KEGG database. Eventually, the druggable proteome has been fetched using sequence similarity with the already available drug targets present in DrugBank database. These druggable proteins were further explored for the structural details to identify drug candidates. Results : A priority list of potential drug targets was provided with the help of the applied method on complete proteome set of the C. difficile. Moreover, the drug like compounds have been screened against the potential drug targets to prioritize potential drug candidates. To facilitate the need for drug targets and therapies, the study proposed five potential protein drug targets out of which three proposed drug targets were subjected to homology modeling to explore their structural and functional activities. Conclusion: In conclusion, we proposed three unique, unexplored drug targets against C. difficile. The structure-based methods were applied and resulted in a list of top scoring compounds as potential inhibitors to proposed drug targets.

Subtractive genomics approach for identification of putative antimicrobial targets in Xanthomonas oryzae pv. oryzae KACC10331

2019 ◽  
Vol 52 (7-8) ◽  
pp. 863-872 ◽  
Author(s):  
Ratna Prabha ◽  
Dhananjaya P. Singh ◽  
Khurshid Ahmad ◽  
S. Prashant Jeevan Kumar ◽  
Pradeep Kumar
Keyword(s):  
Xanthomonas Oryzae ◽  
Subtractive Genomics ◽  
Subtractive Genomics Approach
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