Shapiro Justin A, Wencewicz Timothy A
Department of Chemistry, Washington University in St. Louis , One Brookings Drive, St. Louis, Missouri 63130, United States.
ACS Infect Dis. 2016 Feb 12;2(2):157-68. doi: 10.1021/acsinfecdis.5b00145. Epub 2015 Dec 23.
Pathogenic strains of Acinetobacter baumannii excrete multiple siderophores that enhance iron scavenging from host sources. The oxazoline siderophore pre-acinetobactin undergoes an unusual non-enzymatic isomerization, producing the isoxazolidinone acinetobactin. In this study, we explored the kinetics, mechanism, and biological consequence of this siderophore swapping. Pre-acinetobactin is excreted to the extracellular space where the isomerization to acinetobactin occurs with a pH-rate profile consistent with 5-exo-tet cyclization at C5' with clean stereochemical inversion. Pre-acinetobactin persists at pH <6, and acinetobactin is rapidly formed at pH >7, matching each siderophore's pH preference for iron(III) chelation and A. baumannii growth promotion. Acinetobactin isomerization provides two siderophores for the price of one, enabling A. baumannii to sequester iron over a broad pH range likely to be encountered during the course of an infection.
鲍曼不动杆菌的致病菌株会分泌多种铁载体，这些铁载体可增强从宿主来源获取铁的能力。恶唑啉铁载体前鲍曼不动杆菌素会发生一种不寻常的非酶异构化反应，生成异恶唑烷酮型鲍曼不动杆菌素。在本研究中，我们探究了这种铁载体交换的动力学、机制及生物学后果。前鲍曼不动杆菌素被分泌到细胞外空间，在那里异构化为鲍曼不动杆菌素，其pH速率曲线与C5'处的5-外向-四环化反应一致，且具有明确的立体化学反转。前鲍曼不动杆菌素在pH <6时持续存在，而鲍曼不动杆菌素在pH >7时迅速形成，这与每种铁载体对铁(III)螯合和促进鲍曼不动杆菌生长的pH偏好相匹配。鲍曼不动杆菌素异构化以一份的代价提供了两种铁载体，使鲍曼不动杆菌能够在感染过程中可能遇到的广泛pH范围内螯合铁。
