RESUMO
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
Humanos , Infecções por Bartonella/tratamento farmacológico , Bartonella bacilliformis/efeitos dos fármacos , Antibacterianos/uso terapêutico , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/genética , Reação em Cadeia da Polimerase , Genômica , Bartonella bacilliformis/isolamento & purificação , Bartonella bacilliformis/genéticaAssuntos
Humanos , Infecções por Bartonella/diagnóstico , Infecções por Bartonella/sangue , Bartonella bacilliformis/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/métodos , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Países em Desenvolvimento , Microscopia/métodosRESUMO
Abstract Infective endocarditis due to Bartonella bacilliformis is rare. A 64-year-old woman, without previous heart disease, presented with 6 weeks of fever, myalgias, and arthralgias. A systolic murmur was heard on the tricuspid area upon examination, and an echocardiogram showed endocardial lesions in the right atrium. Bartonella bacilliformis was isolated in blood cultures, defining the diagnosis of infective endocarditis using Duke's criteria. Subsequently, the patient developed clinical and laboratory features compatible with antineutrophil cytoplasmic antibody-associated vasculitis. This case presents an uncommon complication of B. bacilliformis infection associated with the development of systemic vasculitis.