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Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach

BACKGROUND: Carrion’s disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys. The spread of resistant strains underlines the need for novel antimicrobials against B. bacilliformis and related bacterial pathogens. OBJECTIV...

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Autores principales: Farfán-López, Mariella, Espinoza-Culupú, Abraham, García-de-la-Guarda, Ruth, Serral, Federico, Sosa, Ezequiel, Palomino, María Mercedes, Fernández Do Porto, Darío A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Instituto Oswaldo Cruz, Ministério da Saúde 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416641/
https://www.ncbi.nlm.nih.gov/pubmed/32785422
http://dx.doi.org/10.1590/0074-02760200184
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author Farfán-López, Mariella
Espinoza-Culupú, Abraham
García-de-la-Guarda, Ruth
Serral, Federico
Sosa, Ezequiel
Palomino, María Mercedes
Fernández Do Porto, Darío A
author_facet Farfán-López, Mariella
Espinoza-Culupú, Abraham
García-de-la-Guarda, Ruth
Serral, Federico
Sosa, Ezequiel
Palomino, María Mercedes
Fernández Do Porto, Darío A
author_sort Farfán-López, Mariella
collection PubMed
description BACKGROUND: Carrion’s disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys. The spread of resistant strains underlines the need for novel antimicrobials against B. bacilliformis and related bacterial pathogens. OBJECTIVE: The main aim of this study was to integrate genomic-scale data to shortlist a set of proteins that could serve as attractive targets for new antimicrobial discovery to combat B. bacilliformis. METHODS: We performed a multidimensional genomic scale analysis of potential and relevant targets which includes structural druggability, metabolic analysis and essentiality criteria to select proteins with attractive features for drug discovery. FINDINGS: We shortlisted seventeen relevant proteins to develop new drugs against the causative agent of Carrion’s disease. Particularly, the protein products of fabI, folA, aroA, trmFO, uppP and murE genes, meet an important number of desirable features that make them attractive targets for new drug development. This data compendium is freely available as a web server (http://target.sbg.qb.fcen.uba.ar/). MAIN CONCLUSION: This work represents an effort to reduce the costs in the first phases of B. bacilliformis drug discovery.
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spelling pubmed-74166412020-08-19 Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach Farfán-López, Mariella Espinoza-Culupú, Abraham García-de-la-Guarda, Ruth Serral, Federico Sosa, Ezequiel Palomino, María Mercedes Fernández Do Porto, Darío A Mem Inst Oswaldo Cruz Original Article BACKGROUND: Carrion’s disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys. The spread of resistant strains underlines the need for novel antimicrobials against B. bacilliformis and related bacterial pathogens. OBJECTIVE: The main aim of this study was to integrate genomic-scale data to shortlist a set of proteins that could serve as attractive targets for new antimicrobial discovery to combat B. bacilliformis. METHODS: We performed a multidimensional genomic scale analysis of potential and relevant targets which includes structural druggability, metabolic analysis and essentiality criteria to select proteins with attractive features for drug discovery. FINDINGS: We shortlisted seventeen relevant proteins to develop new drugs against the causative agent of Carrion’s disease. Particularly, the protein products of fabI, folA, aroA, trmFO, uppP and murE genes, meet an important number of desirable features that make them attractive targets for new drug development. This data compendium is freely available as a web server (http://target.sbg.qb.fcen.uba.ar/). MAIN CONCLUSION: This work represents an effort to reduce the costs in the first phases of B. bacilliformis drug discovery. Instituto Oswaldo Cruz, Ministério da Saúde 2020-08-10 /pmc/articles/PMC7416641/ /pubmed/32785422 http://dx.doi.org/10.1590/0074-02760200184 Text en https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License
spellingShingle Original Article
Farfán-López, Mariella
Espinoza-Culupú, Abraham
García-de-la-Guarda, Ruth
Serral, Federico
Sosa, Ezequiel
Palomino, María Mercedes
Fernández Do Porto, Darío A
Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach
title Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach
title_full Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach
title_fullStr Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach
title_full_unstemmed Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach
title_short Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach
title_sort prioritisation of potential drug targets against bartonella bacilliformis by an integrative in-silico approach
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416641/
https://www.ncbi.nlm.nih.gov/pubmed/32785422
http://dx.doi.org/10.1590/0074-02760200184
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