RT Journal Article
SR Electronic
T1 Essential Metabolic Routes as a Way to ESKAPE from Antibiotic Resistance
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 817015
DO 10.1101/817015
A1 Angélica Luana C. Barra
A1 Lívia de Oliveira C. Dantas
A1 Luana Galvão Morão
A1 Raíssa F. Gutierrez
A1 Igor Polikarpov
A1 Carsten Wrenger
A1 Alessandro S. Nascimento
YR 2020
UL http://biorxiv.org/content/early/2020/01/13/817015.abstract
AB The antibiotic resistance is a worldwide concern that requires a concerted action from physicians, patients, governmental agencies and academia to prevent infections and the spread of resistance, to track resistant bacteria, to improve the use of current antibiotics and to develop new antibiotics. Despite the efforts spent so far, the current antibiotics in the market are restricted to only five general targets/pathways highlighting the need for basic research focusing on the discovery and evaluation of new potential targets. Here we interrogate two biosynthetic pathways as potentially druggable pathways in bacteria. The biosynthesis pathway for thiamine (vitamin B1), absent in humans, but found in many bacteria, including organisms in the group of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter species) and the biosynthesis pathway for pyridoxal 5’-phosphate and its vitamers (vitamin B6), found in S. aureus. Using current genomic data, we discuss the possibilities of inhibition of enzymes in the pathway and review the current state of the art in the scientific literature.