TY - JOUR
T1 - Prioritisation of potential drug targets against bartonella bacilliformis by an integrative in-silico approach
AU - Farfán-López, Mariella
AU - Espinoza-Culupú, Abraham
AU - García-De-la-guarda, Ruth
AU - Serral, Federico
AU - Sosa, Ezequiel
AU - Palomino, María Mercedes
AU - Porto, Darío A.Fernández Do
N1 - Publisher Copyright:
© 2020, Fundacao Oswaldo Cruz. All rights reserved.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Bartonella bacilliformis
KW - Carrion’s disease
KW - Drug targets
KW - Metabolic networks
KW - Structurome
UR - http://www.scopus.com/inward/record.url?scp=85089408242&partnerID=8YFLogxK
U2 - 10.1590/0074-02760200184
DO - 10.1590/0074-02760200184
M3 - Artículo
C2 - 32785422
AN - SCOPUS:85089408242
SN - 0074-0276
VL - 115
SP - 1
EP - 11
JO - Memorias do Instituto Oswaldo Cruz
JF - Memorias do Instituto Oswaldo Cruz
IS - 7
M1 - e200184
ER -