Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii

Ticks and tick-borne pathogens (TBPs) continuously causing substantial losses to the public and veterinary health sectors. The identification of putative drug targets and vaccine candidates is crucial to control TBPs. No information has been recorded on designing novel drug targets and vaccine candidates based on proteins. Subtractive proteomics is an in silico approach that utilizes extensive screening for the identification of novel drug targets or vaccine candidates based on the determination of potential target proteins available in a pathogen proteome that may be used effectively to control diseases caused by these infectious agents. The present study aimed to investigate novel drug targets and vaccine candidates by utilizing subtractive proteomics to scan the available proteomes of TBPs and predict essential and non-host homologous proteins required for the survival of these diseases causing agents. Subtractive proteome analysis revealed a list of fifteen essential, non-host homologous, and unique metabolic proteins in the complete proteome of selected pathogens. Among these therapeutic target proteins, three were excluded due to the presence in host gut metagenome, eleven were found to be highly potential drug targets, while only one was found as a potential vaccine candidate against TBPs. The present study may provide a foundation to design potential drug targets and vaccine candidates for the effective control of infections caused by TBPs.

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Identification of putative non-host essential genes and novel drug targets against Acinetobacter baumannii by in silico comparative genome analysis

Microbial Pathogenesis ◽

10.1016/j.micpath.2018.12.015 ◽

2019 ◽

Vol 128 ◽

pp. 28-35 ◽

Cited By ~ 2

Author(s):

Reaz Uddin ◽

Fareha Masood ◽

Syed Sikander Azam ◽

Abdul Wadood

Keyword(s):

Acinetobacter Baumannii ◽

Genome Analysis ◽

In Silico ◽

Drug Targets ◽

Essential Genes ◽

Comparative Genome Analysis ◽

Comparative Genome ◽

Novel Drug ◽

Novel Drug Targets

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Subtractive proteomics and systems biology analysis revealed novel drug targets in Mycoplasma genitalium strain G37

Microbial Pathogenesis ◽

10.1016/j.micpath.2020.104231 ◽

2020 ◽

Vol 145 ◽

pp. 104231

Author(s):

Zhiyuan Yang ◽

Jinpao Hou ◽

Mingdao Mu ◽

Shang Ying Wu

Keyword(s):

Systems Biology ◽

Drug Targets ◽

Mycoplasma Genitalium ◽

Subtractive Proteomics ◽

Novel Drug ◽

Novel Drug Targets

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Chlamydia trachomatis core genome data mining for promising novel drug targets and chimeric vaccine candidates identification

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2021.104701 ◽

2021 ◽

pp. 104701

Author(s):

Muneeba Aslam ◽

Muhammad Shehroz ◽

Fawad Ali ◽

Asad Zia ◽

Sadia Pevaiz ◽

...

Keyword(s):

Data Mining ◽

Chlamydia Trachomatis ◽

Drug Targets ◽

Core Genome ◽

Vaccine Candidates ◽

Genome Data ◽

Novel Drug ◽

Chimeric Vaccine ◽

Novel Drug Targets

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IN SILICO IDENTIFICATION OF NOVEL DRUG TARGETS IN ACINETOBACTER BAUMANNII BY SUBTRACTIVE GENOMIC APPROACH

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i3.22105 ◽

2018 ◽

Vol 11 (3) ◽

pp. 230 ◽

Cited By ~ 3

Author(s):

Meenu Goyal ◽

Citu Citu ◽

Nidhi Singh

Keyword(s):

Acinetobacter Baumannii ◽

In Silico ◽

Metabolic Pathways ◽

Drug Targets ◽

Potential Drug ◽

Homologous Proteins ◽

Essential Proteins ◽

Novel Drug ◽

Potential Drug Targets ◽

Novel Drug Targets

Objective: Multiple drug resistance (MDR) in bacteria, particularly Gram-negative bacilli, has significantly hindered the treatment of infections caused by these bacteria. This results in the need for identifying new drugs and drug targets for these bacteria. The objective of this study was to identify novel drug targets in Acinetobacter baumannii which has emerged as a medically important pathogen due to an increasing number of infections caused by it and its MDR property.Methods: In our study, we implemented in silico subtractive genomics approach to identify novel drug targets in A. baumannii American type culture collection 17978. Various databases and online software were used to build a systematic workflow involving comparative genomics, metabolic pathways analysis, and drug target prioritization to identify pathogen-specific novel drug targets.Results: First, 458 essential proteins were retrieved from a database of essential genes, and by performing BLASTp against Homo sapiens, 246 human non-homologous essential proteins were selected of 458 proteins. Metabolic pathway analysis performed by Kyoto Encyclopedia of Genes and Genomes–Kyoto Automatic Annotation Server revealed that these 246 essential non-homologous proteins were involved in 66 metabolic pathways. Among these metabolic pathways, 12 pathways were found to be unique to Acinetobacter that involved 37 non-homologous essential proteins. Of these essential non-homologous proteins, 19 proteins were found in common as well as unique metabolic pathways and only 18 proteins were unique to Acinetobacter. Finally, these target proteins were filtered to 9 potential targets, based on subcellular localization and assessment of druggability using Drug bank, ChEMBL, and literature.Conclusion: Our study identified nine potential drug targets which are novel targets in A. baumannii and can be used for designing drugs against these proteins. These drugs will be pathogen specific with no side effects on human host, as the potential drug targets are human non-homologous.

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