Nature Chemical Biology:发现一种新型抗生素

2009年10月21日 23:16  点击:[]

对医院和卫生机构来说,抗生素抗性是一个重要的问题。尽管对治疗方法不断有新的需求,但在过去的40年中也只开发了两类新的抗生素。

现在,麦克马斯特大学的研究人员发现了一种新的化合物,并开始开发了一种新的抵抗感染的干预方法。

这项研究的负责人Eric Brown教授介绍说,他们已经识别了一种新型的化合物,该物质以一种与现有抗生素不同的方式靶向定位药物抑制细菌。这项发现将引导新的抗菌疗法,以克服特殊类型微生物的抗生素抗性。

这项研究结果发布在9月27日的Nature Chemical Biology上。

该研究小组使用高通量扫描发现了这种化合物。这个方法允许科学家在寻找新的杀菌小分子的同时,可以获得其分子机制和相关的通路信息。

现在的抗生素通常是通过阻碍细菌细胞壁,DNA或蛋白质的形成来消灭细菌,而这种新的化合物即MAC13243能通过直接阻碍细菌细胞表面形成过程中某一个特定的步骤来破坏细胞。此外,该过程至今还未被作为抗生素的靶标。

接下来研究人员将进行试验以确定这种化合物能否成为抗菌药物。(生物谷bioon.com)

生物谷推荐原始出处:

Nature Chemical Biology27 September 2009 | doi:10.1038/nchembio.221

Chemical genomics in Escherichia coli identifies an inhibitor of bacterial lipoprotein targeting

Ranjana Pathania1,2,4, Soumaya Zlitni1,2, Courtney Barker1,2, Rahul Das3, David A Gerritsma2,3, Julie Lebert2,3, Emilia Awuah2,3, Giuseppe Melacini1,3, Fred A Capretta2,3 & Eric D Brown1,2

One of the most significant hurdles to developing new chemical probes of biological systems and new drugs to treat disease is that of understanding the mechanism of action of small molecules discovered with cell-based small-molecule screening. Here we have assembled an ordered, high-expression clone set of all of the essential genes from Escherichia coli and used it to systematically screen for suppressors of growth inhibitory compounds. Using this chemical genomic approach, we demonstrate that the targets of well-known antibiotics can be identified as high copy suppressors of chemical lethality. This approach led to the discovery of MAC13243, a molecule that belongs to a new chemical class and that has a unique mechanism and promising activity against multidrug-resistant Pseudomonas aeruginosa. We show that MAC13243 inhibits the function of the LolA protein and represents a new chemical probe of lipoprotein targeting in bacteria with promise as an antibacterial lead with Gram-negative selectivity.

1 Department of Biochemistry and Biomedical Sciences.

Michael G. DeGroote Institute of Infectious Disease Research.

2 Department of Chemistry, McMaster University, Hamilton, Ontario, Canada.

3 Present address: Department of Biotechnology, Indian Institute of Technology, Roorkee Uttaranchal, India.

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