Identification of novel drug targets for humans and potential vaccine targets for cattle by subtractive genomic analysis of Brucella abortus strain 2308

Mahmud, Araf; Khan, Md. Tahsin; Iqbal, Asif

doi:10.1016/j.micpath.2019.103731

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…The strategy of subtractive genome/proteome analysis was pursued to identify potential drug (and vaccine) targets to treat B. abortus in humans and cattle [85]. The rationale was to single out potentially druggable proteins essential for B. abortus that are absent in the host organism.…”

Section: Antibiotic Targets and Resistancementioning

confidence: 99%

Proteomics of Brucella

Poetsch

Marchesini

2020

Proteomes

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Brucella spp. are Gram negative intracellular bacteria responsible for brucellosis, a worldwide distributed zoonosis. A prominent aspect of the Brucella life cycle is its ability to invade, survive and multiply within host cells. Comprehensive approaches, such as proteomics, have aided in unravelling the molecular mechanisms underlying Brucella pathogenesis. Technological and methodological advancements such as increased instrument performance and multiplexed quantification have broadened the range of proteome studies, enabling new and improved analyses, providing deeper and more accurate proteome coverage. Indeed, proteomics has demonstrated its contribution to key research questions in Brucella biology, i.e., immunodominant proteins, host-cell interaction, stress response, antibiotic targets and resistance, protein secretion. Here, we review the proteomics of Brucella with a focus on more recent works and novel findings, ranging from reconfiguration of the intracellular bacterial proteome and studies on proteomic profiles of Brucella infected tissues, to the identification of Brucella extracellular proteins with putative roles in cell signaling and pathogenesis. In conclusion, proteomics has yielded copious new candidates and hypotheses that require future verification. It is expected that proteomics will continue to be an invaluable tool for Brucella and applications will further extend to the currently ill-explored aspects including, among others, protein processing and post-translational modification.

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Section: Antibiotic Targets and Resistancementioning

confidence: 99%

Proteomics of Brucella

Poetsch

Marchesini

2020

Proteomes

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“…Moreover, the remaining eight proteins (seven characterised proteins and one uncharacterised protein) that showed no similarity with any known drug/drug targets in the DrugBank database were termed novel drug targets ( Table 3 ), and the characterised proteins were selected for further analysis. A similar approach has been used by different authors to detect novel drug targets against different pathogens [ 23 , 24 , 31 ]. The unique metabolic pathways of these proposed novel drug targets include the following: microbial metabolism in diverse environments, two-component system, biosynthesis of secondary metabolites, O-antigen nucleotide sugar biosynthesis, quorum sensing, bacterial secretion, sulphur relay system, and methane metabolism ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium

2021

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Mycoplasma genitalium infection is a sexually transmitted infection that causes urethritis, cervicitis, and pelvic inflammatory disease (PID) in men and women. The global rise in antimicrobial resistance against recommended antibiotics for the treatment of M. genitalium infection has triggered the need to explore novel drug targets against this pathogen. The application of a bioinformatics approach through subtractive genomics has proven highly instrumental in predicting novel therapeutic targets against a pathogen. This study aimed to identify essential and non-homologous proteins with unique metabolic pathways in the pathogen that could serve as novel drug targets. Based on this, a manual comparison of the metabolic pathways of M. genitalium and the human host was done, generating nine pathogen-specific metabolic pathways. Additionally, the analysis of the whole proteome of M. genitalium using different bioinformatics databases generated 21 essential, non-homologous, and cytoplasmic proteins involved in nine pathogen-specific metabolic pathways. The further screening of these 21 cytoplasmic proteins in the DrugBank database generated 13 druggable proteins, which showed similarity with FDA-approved and experimental small-molecule drugs. A total of seven proteins that are involved in seven different pathogen-specific metabolic pathways were finally selected as novel putative drug targets after further analysis. Therefore, these proposed drug targets could aid in the design of potent drugs that may inhibit the functionality of these pathogen-specific metabolic pathways and, as such, lead to the eradication of this pathogen.

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“…Moreover, MS/MS analysis identified five B. abortus S19 proteins (invasion protein B, Sod, Dps, Ndk and Bfr), which were related with antigenicity in naturally infected cattle. In a more recent study [ 119 ], non-homologous proteins to cattle and humans were selected for metabolic analysis. Only three membrane proteins (ABC transporter permease, acriflavine resistance protein B, penicillin-binding protein 2) were found to be potential candidates for inclusion in vaccines with cattle as the host, whereas one membrane protein (ABC transporter permease) was selected as novel drug target with humans as the host [ 119 ].…”

Section: Proteomics Applications In Zoonotic Infectionsmentioning

confidence: 99%

“…In a more recent study [ 119 ], non-homologous proteins to cattle and humans were selected for metabolic analysis. Only three membrane proteins (ABC transporter permease, acriflavine resistance protein B, penicillin-binding protein 2) were found to be potential candidates for inclusion in vaccines with cattle as the host, whereas one membrane protein (ABC transporter permease) was selected as novel drug target with humans as the host [ 119 ]. The results of this study could facilitate the discovery and release of new and effective drugs and would help designing and producing potent vaccines against the pathogen.…”

Section: Proteomics Applications In Zoonotic Infectionsmentioning

confidence: 99%

Applied Proteomics in ‘One Health’

Katsarou

Billinis

Galamatis³

et al. 2021

Proteomes

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‘One Health’ summarises the idea that human health and animal health are interdependent and bound to the health of ecosystems. The purpose of proteomics methodologies and studies is to determine proteins present in samples of interest and to quantify changes in protein expression during pathological conditions. The objectives of this paper are to review the application of proteomics technologies within the One Health concept and to appraise their role in the elucidation of diseases and situations relevant to One Health. The paper develops in three sections. Proteomics Applications in Zoonotic Infections part discusses proteomics applications in zoonotic infections and explores the use of proteomics for studying pathogenetic pathways, transmission dynamics, diagnostic biomarkers and novel vaccines in prion, viral, bacterial, protozoan and metazoan zoonotic infections. Proteomics Applications in Antibiotic Resistance part discusses proteomics applications in mechanisms of resistance development and discovery of novel treatments for antibiotic resistance. Proteomics Applications in Food Safety part discusses the detection of allergens, exposure of adulteration, identification of pathogens and toxins, study of product traits and characterisation of proteins in food safety. Sensitive analysis of proteins, including low-abundant ones in complex biological samples, will be achieved in the future, thus enabling implementation of targeted proteomics in clinical settings, shedding light on biomarker research and promoting the One Health concept.

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Identification of novel drug targets for humans and potential vaccine targets for cattle by subtractive genomic analysis of Brucella abortus strain 2308

Cited by 14 publications

References 25 publications

Proteomics of Brucella

Proteomics of Brucella

Subtractive Genomics Approach for Identification of Novel Therapeutic Drug Targets in Mycoplasma genitalium

Applied Proteomics in ‘One Health’

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