Abstract：
Infections due to Acinetobacter baumannii (A. baumannii) are rapidly increasing worldwide and consequently therapeutic options for treatment are limited. The emergence of multi drug resistant (MDR) strains has rendered available antibiotics ineffective, necessitating the urgent discovery of new drugs and drug targets. The vitamin B6 biosynthetic pathway has been considered as a potential antibacterial drug target but it is as yet uncharacterized for A. baumannii. In the current work, we have carried out in silico and biochemical characterization of Erythrose-4-phosphate dehydrogenase (E4PDH) (EC 1.2.1.72). This enzyme catalyzes the first step in the deoxyxylulose-5-phosphate (DXP) dependent Vitamin B6 biosynthetic pathway i.e. the conversion of d-erythrose-4-phosphate (E4P) to 4-Phosphoerythronate. E4PDH also possesses an additional activity whereby it can catalyze the conversion of Glyceraldehyde-3-phosphate (G3P) to 1,3 bisphosphoglycerate (1,3BPG). Our studies have revealed that this enzyme exhibits an alternate moonlighting function as a cell surface receptor for the human iron transport proteins transferrin (Tf) and lactoferrin (Lf). The present work reports the internalization of Tf and consequent iron acquisition as an alternate strategy for iron acquisition. Given its essential role in two crucial pathways i.e. metabolism and iron acquisition, A. baumannii E4PDH may play a vital role in bacterial pathogenesis.
摘要：
鲍曼不动杆菌感染（A.鲍曼不动杆菌）在全球范围内迅速增加，因此治疗的治疗选择有限。多重耐药（MDR）菌株的出现使可用的抗生素无效，迫切需要发现新的药物和药物靶点。维生素B6生物合成途径已被认为是潜在的抗菌药物靶标,但其对于鲍曼不动杆菌尚未表征。在目前的工作中,我们已经进行了红系-4-磷酸脱氢酶（E4PDH）（EC1.2.1.72）的计算机和生化表征。该酶催化脱氧木酮糖-5-磷酸(DXP)依赖性维生素B6生物合成途径中的第一步,即d-赤藓糖-4-磷酸(E4P)转化为4-磷酸赤藓酸盐。E4PDH还具有额外的活性,由此它可以催化甘油醛-3-磷酸(G3P)向1,3双磷酸甘油酸(1,3BPG)的转化。我们的研究表明，该酶具有替代的月光作用，可作为人类铁转运蛋白转铁蛋白（Tf）和乳铁蛋白（Lf）的细胞表面受体。本工作报告了Tf的内部化和随之而来的铁收购作为铁收购的替代策略。鉴于其在两个关键途径，即代谢和铁获取中的重要作用，鲍曼不动杆菌E4PDH可能在细菌发病机理中起重要作用。
