Anthracimycin, a Potent Anthrax Antibiotic from a Marine-Derived Actinomycete
Anthracimycin, a Potent Anthrax Antibiotic from a Marine-Derived Actinomycete
复制标题
DOI：
10.1002/anie.201302749
复制
发表时间：
2013-07-22
影响因子：
16.6
通讯作者：
Fenical, William
中科院分区：
文献类型：
--
作者：
Jang, Kyoung Hwa;Nam, Sang-Jip;Fenical, William
人类传染病炭疽是由革兰氏阳性细菌炭疽芽孢杆菌引起的。这种疾病在处理受感染的农场动物的人身上最常见，也被用作生物恐怖主义武器。2001年，就在世贸中心遭到袭击一周后，炭疽病毒通过美国邮政系统故意传播，通过邮寄含有炭疽芽孢粉末状的信件。这导致了22例炭疽感染，最终夺去了5人的生命根据接触方法（吸入孢子、直接接触细菌等）不同，炭疽芽胞杆菌感染需要使用各种抗生素进行长时间治疗，通常需要6个月。肺部形式的炭疽被认为是医疗紧急情况，可能需要持续静脉注射强效抗生素治疗。在潜在的生物恐怖袭击中，暴露于炭疽杆菌的个体将在发病前被给予抗生素。已经研制出一种疫苗，但尚未向公众提供鉴于这种疾病的严重性，以及它可以通过气溶胶传播的事实，开发有效的新抗生素武器库仍然是公共的高度优先事项。作为一种新兴的微生物抗生素资源，海洋微生物，特别是深海中特有的海洋微生物是我们研究的重点。从加利福尼亚州圣巴巴拉附近的近岸海洋沉积物中分离出的一种链霉菌（我们的菌株CNH365）的检测表明，培养提取物在肉汤稀释试验中对炭疽杆菌和耐甲氧西林金黄色葡萄球菌具有显著的活性。随后，根据抗菌活性对提取物进行分离，得到了一种纯抗生素——红霉素(1)。分离得到白色固体的红霉素，用HR-ESIMS （- 0.2 mmu）分析其分子式为C25H32O4。1的13C核磁共振谱（表1）显示了两个酮类官能团，一个酯或内酯基团（δC 194.1, 190.9和168.9），芳香/烯烃区9个甲基碳信号（δC 140~ 103）和一个氧甲基
The human infectious disease Anthrax is caused by the spore-forming, Gram-positive bacterium Bacillus anthracis. The disease, which is most common in those that handle infected farm animals, has also been used as a bioterrorism weapon. In 2001, just a week after the World Trade Center attacks, Anthrax was deliberately spread through the US postal system by sending letters with powdered B. anthracis spores. This caused 22 cases of Anthrax infection and ultimately claimed five lives.[1] Depending upon the method of exposure (inhalation of spores, direct bacterial contact, etc.) B. anthracis infections can require prolonged treatment often for 6 months with a variety of antibiotics. The pulmonary form of Anthrax is considered a medical emergency that may require continuous intravenous therapy with potent antibiotics. In a potential bioterrorism attack, individuals exposed to B. anthracis will be given antibiotics prior to onset of the illness. A vaccine has been developed but is not yet available to the general public.[2] Given the severity of this disease, and the fact that it can be spread by aerosol dispersal, the development of an effective arsenal of new antibiotics remains a high public priority.As a new, developing resource for microbial antibiotics, we have focused our efforts on marine microorganisms, particularly those that are in the deep oceans and specific to the marine environment. Examination of a Streptomyces species (our strain CNH365), isolated from near-shore marine sediments found near Santa Barbara, CA, showed that culture extracts possessed significant activity against B. anthracis and methicillin-resistant Staphylococcus aureus in broth dilution assays. Subsequent fractionation of the extract following antibacterial activities yielded a pure antibiotic, anthracimycin (1). Anthracimycin was isolated as a white solid that analyzed for the molecular formula C25H32O4 by HR-ESIMS analysis (− 0.2 mmu). The 13C NMR spectrum of 1 (Table 1) displayed what appeared to be two ketone functionalities, one ester or lactone group (δC 194.1, 190.9, and 168.9), nine methine carbon signals in the aromatic/olefinic region (δC 140~ 103), and an oxymethine