Abstract

The rise of antibacterial-resistant bacteria is a major problem in the United States of America and around the world. Millions of patients are infected with antimicrobial resistant bacteria each year. Novel antibacterial agents are needed to combat the growing and present crisis. Acetyl-CoA carboxylase (ACC), the multi-subunit complex which catalyses the first committed step in fatty acid synthesis, is a validated target for antibacterial agents. However, there are at present, no commercially available antibiotics that target ACC. Ethyl 4-[[2-chloro-5-(phenylcarbamoyl)phenyl]sulfonylamino]benzoate (SABA1) is a compound that has been shown to have antibacterial properties against Pseudomonas aeruginosa and Escherichia coli. SABA1 inhibits biotin carboxylase (BC), the enzyme that catalyses the first half reaction of ACC. SABA1 inhibits BC via an atypical mechanism. It binds in the biotin binding site in the presence of ADP. SABA1 represents a potentially new class of antibiotics that can be used to combat the antibacterial resistance crisis.

摘要

耐药细菌的兴起是美国和世界各地的一个主要问题。每年有数百万患者感染抗菌素耐药菌。需要新型抗菌剂来应对日益严重的和当前的危机。乙酰辅酶A羧化酶 (ACC) 是一种多亚基复合物，可催化脂肪酸合成的第一步，是经过验证的抗菌剂靶标。然而，目前还没有针对 ACC 的市售抗生素。4-[[2-chloro-5-(phenylcarbamoyl)phenyl]sulfonylamino]benzoate (SABA1) 是一种化合物，已被证明对铜绿假单胞菌和大肠杆菌具有抗菌特性. SABA1 抑制生物素羧化酶 (BC)，该酶催化 ACC 的前半部分反应。SABA1 通过非典型机制抑制 BC。它在 ADP 存在下结合在生物素结合位点。SABA1 代表了一类潜在的新型抗生素，可用于对抗细菌耐药性危机。