對醫(yī)院和衛(wèi)生機構來說，抗生素抗性是一個重要的問題,。盡管對治療方法不斷有新的需求，但在過去的40年中也只開發(fā)了兩類新的抗生素,。
現(xiàn)在,，麥克馬斯特大學的研究人員發(fā)現(xiàn)了一種新的化合物，并開始開發(fā)了一種新的抵抗感染的干預方法,。
這項研究的負責人Eric Brown教授介紹說,，他們已經(jīng)識別了一種新型的化合物，該物質(zhì)以一種與現(xiàn)有抗生素不同的方式靶向定位藥物抑制細菌,。這項發(fā)現(xiàn)將引導新的抗菌療法,，以克服特殊類型微生物的抗生素抗性。
這項研究結(jié)果發(fā)布在9月27日的Nature Chemical Biology上,。
該研究小組使用高通量掃描發(fā)現(xiàn)了這種化合物,。這個方法允許科學家在尋找新的殺菌小分子的同時，可以獲得其分子機制和相關的通路信息,。
現(xiàn)在的抗生素通常是通過阻礙細菌細胞壁，DNA或蛋白質(zhì)的形成來消滅細菌,，而這種新的化合物即MAC13243能通過直接阻礙細菌細胞表面形成過程中某一個特定的步驟來破壞細胞,。此外，該過程至今還未被作為抗生素的靶標,。
接下來研究人員將進行試驗以確定這種化合物能否成為抗菌藥物,。（生物谷bioon.com）
生物谷推薦原始出處：
Nature Chemical Biology 27 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.
