Target-Pathogen: a bioinformatic tool to prioritize proteic drug targets in pathogens

EZEQUIEL JORGE SOSA ; GERMAN F BURGUENER; ANDRÉS FERNÁNDEZ BENEVENTO; FEDERICO SERRAL; MARCELO MARTÍ; ADRIAN G TURJANSKI ; DARIO A FERNANDEZ DO PORTO

Congreso; XXIV Congreso Latinoamericano de Microbiología; 2018

Asociación Latinoamericana de Microbiología

The successful use of antibiotics has been facing challenges because microbial pathogens are developing various formsof resistance in the last decades. Despite this critical situation, new drug development projects have been inadequatefor reasons ranging from bad selection of targets to reduced antimicrobial drug discovery efforts by pharmaceuticalcompanies. Currently, it is accepted that identification and validation of appropriate targets are critical steps for designingnew drugs. Here, we present Target-Pathogen (http://target.sbg.qb.fcen.uba.ar/patho), an online database that allowsgenome wide target ranking and identification. It integrates essentiality, metabolic role, functional annotation, structuraldruggability data, and allows data upload for other experimentally obtained or other calculated properties. Also, itpermits each user to define a scoring function, to sort / prioritize their protein or pathways search results, according toall the integrated data. In this work we will share our last target prioritization study in Klebsiella pneumoniae KP13, wereTarget-Pathogen gave full support to the methodology followed. Twenty-nine proteins with desirable characteristicsfrom a drug development perspective were shortlisted, which participate in important processes such as lipid synthesis,cofactor production, and core metabolism. Among that results, we highlight fabB, fabI and fabH genes, a subset of thefatty acid elongation pathway and lpxC, involved in the first two steps of lipid A biosynthesis