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.
Highlights
Carrion’s disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys
Generation of models based on structural homology - Since no crystallised Bartonella bacilliformis (Bb) protein structures were found deposited in the Protein Data Bank (PDB) homology-based models were built for all proteome sequences using MODELLER when the adequate template was available as described before.[9,11,17] Briefly, protein sequences were PSI-BLASTed (-num_iterations 3 and -e 1e-05) against the UniRef50
Structural domains were first grouped into two categories considering only the structural models obtained from our work scheme, since the Protein Data Bank (PDB) does not feature any information on experimentally crystallised Bb USM-LMMB07 proteins
Summary
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
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