Genome Subtraction and Comparison for the Identification of Novel Drug Targets against Mycobacterium avium subsp. hominissuis

Mycobacterium avium complex (MAC) is a major cause of non-tuberculous pulmonary and disseminated diseases worldwide, inducing bronchiectasis, and affects HIV and immunocompromised patients. In MAC, Mycobacterium avium subsp. hominissuis is a pathogen that infects humans and mammals, and that is why it is a focus of this study. It is crucial to find essential drug targets to eradicate the infections caused by these virulent microorganisms. The application of bioinformatics and proteomics has made a significant impact on discovering unique drug targets against the deadly pathogens. One successful bioinformatics methodology is the use of in silico subtractive genomics. In this study, the aim was to identify the unique, non-host and essential protein-based drug targets of Mycobacterium avium subsp. hominissuis via in silico a subtractive genomics approach. Therefore, an in silico subtractive genomics approach was applied in which complete proteome is subtracted systematically to shortlist potential drug targets. For this, the complete dataset of proteins of Mycobacterium avium subsp. hominissuis was retrieved. The applied subtractive genomics method, which involves the homology search between the host and the pathogen to subtract the non-druggable proteins, resulted in the identification of a few prioritized potential drug targets against the three strains of M. avium subsp. Hominissuis, i.e., MAH-TH135, OCU466 and A5. In conclusion, the current study resulted in the prioritization of vital drug targets, which opens future avenues to perform structural as well as biochemical studies on predicted drug targets against M. avium subsp. hominissuis.

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

Bioinformation ◽

10.6026/97320630015018 ◽

2019 ◽

Vol 15 (1) ◽

pp. 18-25 ◽

Cited By ~ 2

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

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

Letters in Drug Design & Discovery ◽

10.2174/1570180818666210930160128 ◽

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.

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

Bioinformation ◽

10.6026/97320630015025 ◽

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

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Prioritization of potential drug targets against P. aeruginosa by core proteomic analysis using computational subtractive genomics and Protein-Protein interaction network

Computational Biology and Chemistry ◽

10.1016/j.compbiolchem.2018.02.017 ◽

2018 ◽

Vol 74 ◽

pp. 115-122 ◽

Cited By ~ 17

Author(s):

Reaz Uddin ◽

Faiza Jamil

Keyword(s):

Protein Interaction ◽

Protein Interaction Network ◽

Proteomic Analysis ◽

Drug Targets ◽

Interaction Network ◽

Potential Drug ◽

Protein Protein Interaction ◽

Subtractive Genomics ◽

Potential Drug Targets ◽

Protein Protein Interaction Network

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In Silico Carborane Docking to Proteins and Potential Drug Targets

Journal of Chemical Information and Modeling ◽

10.1021/ci200216z ◽

2011 ◽

Vol 51 (8) ◽

pp. 1882-1896 ◽

Cited By ~ 28

Author(s):

Matteo Calvaresi ◽

Francesco Zerbetto

Keyword(s):

In Silico ◽

Drug Targets ◽

Potential Drug ◽

Potential Drug Targets

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Subtractive Genomics Approach for in Silico Identification and Characterization of Novel Drug Targets in Neisseria Meningitides Serogroup B

Journal of Computer Science & Systems Biology ◽

10.4172/jcsb.1000038 ◽

2009 ◽

Vol 02 (05) ◽

Cited By ~ 9

Author(s):

Aditya Narayan Sarangi

Keyword(s):

In Silico ◽

Drug Targets ◽

Neisseria Meningitides ◽

Subtractive Genomics ◽

In Silico Identification ◽

Subtractive Genomics Approach ◽

Novel Drug ◽

Identification And Characterization ◽

Novel Drug Targets

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In Silico identification of potential drug targets by subtractive genome analysis of Enterococcus faecium DO

10.1101/2020.02.14.948232 ◽

2020 ◽

Author(s):

Marwah Karim ◽

MD Nazrul Islam ◽

G. M. Nurnabi Azad Jewel

Keyword(s):

Alcohol Dehydrogenase ◽

Enterococcus Faecium ◽

In Silico ◽

Drug Targets ◽

3D Structure ◽

Comparative Genomic ◽

Therapeutic Drug ◽

Potential Drug ◽

Novel Drug ◽

Potential Drug Targets

AbstractOnce believed to be a commensal bacteria, Enterococcus faecium has recently emerged as an important nosocomial pathogen worldwide. A recent outbreak of E. faecium unrevealed natural and in vitro resistance against a myriad of antibiotics namely ampicillin, gentamicin and vancomycin due to over-exposure of the pathogen to these antibiotics. This fact combined with the ongoing threat demands the identification of new therapeutic targets to combat E. faecium infections.In this present study, comparative proteome analysis, subtractive genomic approach, metabolic pathway analysis and additional drug prioritizing parameters were used to propose a potential novel drug targets for E. faecium strain DO. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified a total of 207 putative target proteins in E. faecium DO that showed no similarity to human proteins. Among them 105 proteins were identified as essential novel proteins that could serve as potential drug targets through further bioinformatic approaches; such as-prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characterization. Eventually 19 non-homologous essential proteins of E. faecium DO were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets. Among these targets aldehyde-alcohol dehydrogenase was found to be involved in maximum pathways, and therefore, was chosen as novel drug target. Interestingly, aldehyde-alcohol dehydrogenase enzyme contains two domains namely acetaldehyde dehydrogenase and alcohol dehydrogenase, on which a 3D structure homology modeling and in silico molecular docking were performed. Finally, eight molecules were confirmed as the most suitable ligands for aldehyde-alcohol dehydrogenase and hence proposed as the potential inhibitors of this target.In conclusion, being human non-homologous, aldehyde-alcohol dehydrogenase protein can be targeted for potential therapeutic drug development in future. However, laboratory based experimental research should be performed to validate our findings in vivo.

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