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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.
Afiliação
  • Farfán-López M; Laboratorio de Microbiología Molecular y Biotecnología, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • Espinoza-Culupú A; Laboratorio de Microbiología Molecular y Biotecnología, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • García-de-la-Guarda R; Laboratorio de Microbiología Molecular y Biotecnología, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • Serral F; Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Sosa E; Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Palomino MM; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Fernández Do Porto DA; Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Mem Inst Oswaldo Cruz ; 115: e200184, 2020.
Article em En | MEDLINE | ID: mdl-32785422
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Bartonella / Bartonella bacilliformis / Antibacterianos Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Bartonella / Bartonella bacilliformis / Antibacterianos Idioma: En Ano de publicação: 2020 Tipo de documento: Article