布兰迪斯大学（Brandeis University）和德州大学的生化学家们通过X射线结晶方式获得了一种可以阻止某些细菌在植物动物和人身上传播的关键性酶quorum-quenching N-acyl homoserine lactone hydrolase的三维结构。这种酶在之前的研究中证明可以大量降低马铃薯腐病（soft rot）。
这种酶通过扰乱某些细菌对其群体生长数量的感知能力来起作用——这一感知能力是启动细菌毒性基因表达的关键。为了感知到群体数量，某些细菌会产生一种叫做N-acyl homoserine lactones的小分子，这种小分子浓度与细菌数量成正比例，当达到了一个浓度后，就会开启一些细菌毒性基因表达。
这一发表在8月30号PNAS上的研究结果有利于科学家们研究像鼻疽病（glanders）这样的动物病菌威胁或者像囊性纤维性变病（cystic fibrosis）之类的疾病。
原文：Liu D, Lepore BW, Petsko GA, Thomas PW, Stone EM, Fast W, Ringe D. Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis.
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11882-7 可免费下载全文
相关文章：
Geisenberger O, Givskov M, Riedel K, Hoiby N, Tummler B, Eberl L. Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis. FEMS Microbiol Lett. 2000 Mar 15;184(2):273-8.
英文报道：
A team of biomedical researchers from Brandeis University and the University of Texas at Austin has determined the first 3-dimensional structure of an enzyme that may be pivotal in preventing certain bacterial infections in plants, animals and humans, according to a study published in the Proceedings of the National Academy of Sciences.
The enzyme had already been shown in previous studies to significantly decrease soft rot in potato plants. The Brandeis and University of Texas team purified the enzyme and identified its structure using X-ray crystallography, an essential step toward developing drugs that may reduce the pathogenicity of bacteria involved in biowarfare threats such as glanders and diseases such as cystic fibrosis.
"This study represents a significant advance in understanding how this enzyme can prevent certain bacteria from becoming virulent," explained Dagmar Ringe of the Rosenstiel Basic Medical Sciences Research Center at Brandeis University. "One of the promising aspects of potential therapies based on this enzyme is that it targets a different pathway than current antibiotics."
The enzyme works by disrupting the ability of certain bacteria to sense their own population growth - the key to triggering genes that can increase virulence. In order to sense the size of their own populations, certain bacteria produce small molecules called N-acyl homoserine lactones. The concentrations of these lactones increase along with the growth of the bacterial population. After reaching a threshold concentration, the lactones can "turn on" a variety of genes, often increasing the virulence of the accumulating bacteria.
This population-sensing results in a type of bacterial "group think" because certain genes are not turned on until a minimum number of bacteria are present. Hence, this phenomenon is called quorum-sensing.
"Being able to disrupt quorum-sensing in these organisms could potentially augment our current treatments, and knowing the structure of this quorum-quenching enzyme will greatly help in developing more effective enzymes for this type of application," explained Walter Fast, assistant professor in the College of Pharmacy at the University of Texas at Austin.
In addition to treating plant pathogens, the hope is that these quorum-quenching enzymes may eventually be developed for use in treating human and animal pathogens that also rely on quorum-sensing for their virulence.
For example, bacterial pathogens such as Burkholderia mallei, which is responsible for the biowarfare threat glanders, and Pseudomonas aeruginosa, which often forms opportunistic infections on the lung surfaces of patients with cystic fibrosis, rely on their quorum-sensing systems to increase their pathogenicity and resistance to antibiotics.
These studies were supported by the National Institutes of Health and the Robert A. Welch Foundation.
