Barra Angélica Luana C, Dantas Lívia de Oliveira C, Morão Luana Galvão, Gutierrez Raíssa F, Polikarpov Igor, Wrenger Carsten, Nascimento Alessandro S
São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil.
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Front Public Health. 2020 Feb 28;8:26. doi: 10.3389/fpubh.2020.00026. eCollection 2020.
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, track resistant bacteria, improve the use of current antibiotics, and 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 (, and sp.) and the biosynthesis pathway for pyridoxal 5'-phosphate and its vitamers (vitamin B6), found in . 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.
抗生素耐药性是一个全球性问题,需要医生、患者、政府机构和学术界共同采取行动,以预防感染和耐药性传播、追踪耐药菌、改善当前抗生素的使用并开发新抗生素。尽管迄今已付出诸多努力,但目前市场上的抗生素仅局限于五个通用靶点/途径,这凸显了开展基础研究以发现和评估新潜在靶点的必要性。在此,我们探究两种生物合成途径作为细菌中潜在的可成药途径。硫胺素(维生素B1)的生物合成途径在人类中不存在,但在许多细菌中存在,包括ESKAPE病原体组中的生物体( 、 和 菌),以及5'-磷酸吡哆醛及其维生素变体(维生素B6)的生物合成途径,在 中发现。利用当前的基因组数据,我们讨论了抑制该途径中酶的可能性,并回顾了科学文献中的当前技术水平。