布蘭迪斯大學(xué)（Brandeis University）和德州大學(xué)的生化學(xué)家們通過(guò)X射線結(jié)晶方式獲得了一種可以阻止某些細(xì)菌在植物動(dòng)物和人身上傳播的關(guān)鍵性酶quorum-quenching N-acyl homoserine lactone hydrolase的三維結(jié)構(gòu),。這種酶在之前的研究中證明可以大量降低馬鈴薯腐?。╯oft rot）。
這種酶通過(guò)擾亂某些細(xì)菌對(duì)其群體生長(zhǎng)數(shù)量的感知能力來(lái)起作用——這一感知能力是啟動(dòng)細(xì)菌毒性基因表達(dá)的關(guān)鍵。為了感知到群體數(shù)量,，某些細(xì)菌會(huì)產(chǎn)生一種叫做N-acyl homoserine lactones的小分子，這種小分子濃度與細(xì)菌數(shù)量成正比例,，當(dāng)達(dá)到了一個(gè)濃度后,，就會(huì)開(kāi)啟一些細(xì)菌毒性基因表達(dá)。
這一發(fā)表在8月30號(hào)PNAS上的研究結(jié)果有利于科學(xué)家們研究像鼻疽?。╣landers）這樣的動(dòng)物病菌威脅或者像囊性纖維性變病（cystic fibrosis）之類(lèi)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 可免費(fèi)下載全文
相關(guān)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.
英文報(bào)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.
