美国东北大学Kim Lewis研究组取得一项新突破。他们的最新研究揭示了针对莱姆病的特异性抗生素。相关论文于2021年10月14日发表在《细胞》杂志上。
研究人员试图探索一种选择性对抗伯氏疏螺旋体的化合物。土壤微生物筛选揭示了一种对螺旋体（包括伯氏疏螺旋体)具有高度选择性的化合物。意外的是，研究发现该化合物是潮霉素A，这是一种由吸水链霉菌产生的已知抗菌剂。潮霉素A靶向核糖体并被伯氏疏螺旋体吸收，这解释了其选择性机制。潮霉素A清除了小鼠体内的伯氏疏螺旋体感染，包括在诱饵中摄取该化合物的动物，并且与临床相关的抗生素相比，其对粪便微生物组的破坏性更小。这种选择性抗生素有望为莱姆病提供更好的治疗选择并在环境中根除它。
据了解，莱姆病呈上升趋势。该病由螺旋体伯氏疏螺旋体引起，仅在美国估计就有500,000人受到该疾病的困扰。目前用于治疗莱姆病的抗生素是广谱的，会破坏微生物组，并选择对非目标细菌产生抗药性。
附：英文原文
Title: A selective antibiotic for Lyme disease
Author: Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V. Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S. Polikanov, Cecily A. Freliech, Julie E. McCarthy, Diane G. Edmondson, Steven J. Norris, Anthony D’Onofrio, Linden T. Hu, Helen I. Zgurskaya, Kim Lewis
Issue&Volume: 2021/10/14
Abstract: Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.
DOI: 10.1016/j.cell.2021.09.011
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01058-8