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. 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.

Caracterización molecular de la nucleoproteína del virus de la rabia en canes procedentes de Arequipa, Perú / Molecular characterization of the rabies virus' nucleoprotein in dogs from Arequipa, Peru

RESUMEN Objetivos. Caracterizar la nucleoproteína (N) y establecer el origen del virus de la rabia en canes procedentes de Arequipa. Materiales y métodos. Se analizaron 30 muestras de tejido nervioso procedentes de los departamentos de Arequipa y Puno. Se extrajo el ARN total de las muestras y se sintetizó ADNc para amplificar el gen de la nucleoproteína, secuenciarlo y realizar el análisis bioinformático. Resultados. Se obtuvo la formación de un grupo definido con respecto al grupo externo (European bat lyssavirus). Este grupo fue clasificado en dos subgrupos, uno constituido por muestras procedentes de Puno y Arequipa (subgrupo A), y otro por muestras de Puno (subgrupo B), observándose una identidad nucleotídica de 99,9% en el subgrupo A. Conclusiones. Los agrupamientos de las secuencias virales muestran que los casos de rabia canina notificados en Arequipa son el resultado de la expansión de rabia canina procedente de la región endémica de Puno.

ABSTRACT Objective . To characterize the nucleoprotein (N) and establish the origin of the rabies virus in dogs coming from Arequipa. Materials and Methods. Thirty samples of nervous tissue from the departments of Arequipa and Puno were analyzed. Total RNA was extracted from the samples and cDNA was synthesized to amplify the nucleoprotein gene, sequence it, and perform bioinformatics analysis. Results . A defined group was formed with respect to the external group (European bat lyssavirus). This group was classified into two subgroups, one constituted by samples coming from Puno and Arequipa (subgroup A), and another one by samples from Puno (subgroup B), exhibiting a nucleotide identity of 99.9% in subgroup A. This group was classified in two subgroups, one constituted by samples coming from Puno and Arequipa (subgroup A), and another one by samples from Puno (subgroup B), observing a nucleotide identity of 99.9% in subgroup A. Conclusions. The groupings of viral sequences show that the cases of canine rabies reported in Arequipa are the result of the expansion of canine rabies from the endemic region of Puno.