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

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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Genome analysis of Chlamydia trachomatis for functional characterization of hypothetical proteins to discover novel drug targets

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2016.12.045 ◽

2017 ◽

Vol 96 ◽

pp. 234-240 ◽

Cited By ~ 8

Author(s):

Ahmad Abu Turab Naqvi ◽

Safikur Rahman ◽

Rubi ◽

Firdaus Zeya ◽

Kundan Kumar ◽

...

Keyword(s):

Chlamydia Trachomatis ◽

Genome Analysis ◽

Drug Targets ◽

Functional Characterization ◽

Hypothetical Proteins ◽

Novel Drug ◽

Novel Drug Targets

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Proteome Exploration of Legionella pneumophila for Identifying Novel Therapeutics: A Hierarchical Subtractive Genomics and Reverse Vaccinology Approach

10.1101/2020.02.03.922864 ◽

2020 ◽

Author(s):

Md Tahsin Khan ◽

Araf Mahmud ◽

Mahmudul Hasan ◽

Kazi Faizul Azim ◽

Musammat Kulsuma Begum ◽

...

Keyword(s):

Legionella Pneumophila ◽

Drug Targets ◽

Binding Interaction ◽

Efficient Treatment ◽

Vaccine Candidates ◽

Novel Therapeutics ◽

Mhc Molecules ◽

Subtractive Genomics ◽

Novel Drug ◽

Novel Drug Targets

AbstractLegionella pneumophila, the causative agent of a serious type of pneumonia (lung infection) called Legionnaires’ disease. It is emerging as an antibacterial resistant strain day by day. Hence, the identification of novel drug targets and vaccine candidates is essential to fight against this pathogen. Herein attempts were taken through subtractive genomics approach on complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total 2930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human non-homologous and pathogen-specific essential proteins, druggability and ‘anti-target’ analysis, prediction of subcellular localization, human microbiome non-homology screening, protein-protein interactions studies in order to find out effective drug and vaccine targets. Only 3 were identified that fulfilled all these criteria and proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as potential vaccine target with better antigenicity score and allowed for further in silico analysis to design a unique multiepitope subunit vaccine against it. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different MHC molecules and human immune TLR2 receptors with minimum deformability at molecular level. The translational potency and microbial expression of the vaccine protein was also analyzed using pET28a(+) vector. The present study aids in the development of novel therapeutics and vaccine candidates for efficient treatment of the infections caused by Legionella pneumophila. However, further wet lab-based investigations and in vivo trials are highly recommended to experimentally validate our prediction.

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Prediction of Novel Drug Targets and Vaccine Candidates against Human Lice (Insecta), Acari (Arachnida), and Their Associated Pathogens

Vaccines ◽

10.3390/vaccines10010008 ◽

2021 ◽

Vol 10 (1) ◽

pp. 8

Author(s):

Abid Ali ◽

Shabir Ahmad ◽

Pedro Machado Medeiros de Albuquerque ◽

Atif Kamil ◽

Fahdah Ayed Alshammari ◽

...

Keyword(s):

Metabolic Pathways ◽

Drug Targets ◽

Babesia Microti ◽

Economic Losses ◽

Borrelia Miyamotoi ◽

Vaccine Candidates ◽

Essential Proteins ◽

Membrane Bound ◽

Novel Drug ◽

Novel Drug Targets

The emergence of drug-resistant lice, acari, and their associated pathogens (APs) is associated with economic losses; thus, it is essential to find new appropriate therapeutic approaches. In the present study, a subtractive proteomics approach was used to predict suitable therapeutics against these vectors and their infectious agents. We found 9701 proteins in the lice (Pediculus humanus var. corporis) and acari (Ixodes scapularis, Leptotrombidium deliense), and 4822 proteins in the proteomes of their APs (Babesia microti, Borreliella mayonii, Borrelia miyamotoi, Borrelia recurrentis, Rickettsia prowazekii, Orientia tsutsugamushi str. Boryong) that were non-homologous to host proteins. Among these non-homologous proteins, 365 proteins of lice and acari, and 630 proteins of APs, were predicted as essential proteins. Twelve unique essential proteins were predicted to be involved in four unique metabolic pathways of lice and acari, and 103 unique proteins were found to be involved in 75 unique metabolic pathways of APs. The sub cellular localization analysis of 115 unique essential proteins of lice and acari and their APs revealed that 61 proteins were cytoplasmic, 42 as membrane-bound proteins and 12 proteins with multiple localization. The druggability analysis of the identified 73 cytoplasmic and multiple localization essential proteins revealed 22 druggable targets and 51 novel drug targets that participate in unique pathways of lice and acari and their APs. Further, the predicted 42 membrane bound proteins could be potential vaccine candidates. Screening of useful inhibitors against these novel targets may result in finding novel compounds efficient for the control of these parasites.

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