119th General Meeting of the KCS

Type Poster Presentation
Area 생명화학
Room No. 포스터발표장
Time 4월 21일 (금요일) 13:00~14:30
Code BIO.P-318
Subject Biochemical characterization of acinetobactin, a major siderophore of Acinetobacter baumannii, and preparation of its analogues with improved chemical stability
Authors 김학중*, 이민욱, 송운영
고려대학교 화학과, Korea
Abstract Since the iron is involved in many functional metabolic processes, its acquisition is essential to maintain the biological processes. However, the human body, one of the habitats of many bacteria, is highly iron-deficient. Therefore, bacteria have developed dedicated iron acquisition system based on the secretion and uptake cycle of small molecules called "siderophores", effective iron chelators. The siderophore-based metabolic mechanism is particularly essential for the survival of the infectious pathogens such as Acinetobacter baumannii. A. baumannii, a Gram-negative bacterium, has recently emerged as one of the most threatening pathogens particularly in the nosocomial settings due to its rapid acquisition of the multidrug resistance. It has been shown that it produce and utilize acinetobactin, fimsbactins, and baumannoferrins as siderophores. Acinetobactin is the major siderophore of A. baumannii, structurally featured by three potential Fe(III) binding moieties; catechol, hydroxamate, and imidazole groups. Previous studies have revealed that the originally reported structure of acinetobactin possessing the oxazoline at its core can be spontaneously rearranged to its isoxazolidinone derivative. Our laboratory have been interested in developing a novel strategy to effectively combat against A. baumannii. In that direction, the employment of "Trojan horse strategy" based on the attachment of antibiotics to acinetobactin has been considered, in which the latter serves as a drug delivery vehicle. For that matter, it is critical to know which of the two structures is the actual siderophore for A. baumannii. To gain some insights into this question, we have prepared acinetobactin as well as systematically designed analogues and characterized their Fe(III) binding and cellular delivery functions. This investigation not only led to the clarification of the physiologically relevant acinetobactin structure, but also revealed several key structural elements for its functionality as a siderophore. Namely, the acinetobactin form possessing the oxazoline core was confirmed to be the physiologically relevant structure. Currently, various structural modifications on this structure are being made to improved its chemical stability as well as the capability to intracellularly delivery the conjugated antibiotics into A. baumannii.
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