西方大學(xué)最新研究發(fā)現(xiàn)了存在于細(xì)菌間的一種新的通訊手段,,通過這種手段洋蔥伯克霍爾德菌(B.cenocepacia)可以聯(lián)合抵御抗生素的作用,。洋蔥伯克霍爾德菌是一種條件致病菌,也是醫(yī)院感染的重要病原菌之一,。它可以導(dǎo)致感染者囊腫性纖維化(CF)或者免疫系統(tǒng)受損,。
洋蔥伯克霍爾德菌對(duì)多種抗菌藥具有天然的耐藥性
Miguel Valvano博士稱,在細(xì)菌種群間,那些對(duì)抗生素抗性較強(qiáng)的細(xì)菌將產(chǎn)生的耐藥小分子與另外一些對(duì)抗生素抗性較弱的細(xì)菌分享,,以使其對(duì)抗生素的耐性更強(qiáng),。這些小分子大都是一些經(jīng)過修飾的氨基酸,它們不但可以保護(hù)那些較為敏感的洋蔥伯克霍爾德菌,,甚至還可以保護(hù)較為常見的CF病原體,,例如銅綠假單胞菌和大腸桿菌等。
“這項(xiàng)研究揭示了一種新的耐藥機(jī)制,,細(xì)菌間通過小分子進(jìn)行化學(xué)信號(hào)傳遞來共同抵御抗生素的作用,。這為以后藥物研發(fā)提供了新的思路,研發(fā)抗生素藥物應(yīng)當(dāng)盡量避免其受這些化學(xué)小分子的作用以便抗生素能有效發(fā)揮藥效,。”Belfast女王大學(xué)的教授兼系主任Valvano教授說道,。
El-Halfaw博士興奮地說:“除了有限的幾類細(xì)菌除外,幾乎所有的細(xì)菌都可以利用和產(chǎn)生這些化學(xué)小分子,,所以我們可以將這種小分子視作一種細(xì)菌間進(jìn)行通訊的語(yǔ)言,。另外,洋蔥伯克霍爾德菌對(duì)抵御抗生素的藥性還有另外一種更高級(jí)的方式,,它們可以通過釋放小分子蛋白與抗生素結(jié)合來降低抗生素的有效性,。”下一步就是找到解決方法來抑制這種現(xiàn)象的產(chǎn)生。
這項(xiàng)研究是由西方大學(xué)負(fù)責(zé)的,,由加拿大囊腫性纖維化基金會(huì)和居里夫人基金會(huì)資助的,。(生物谷 Bioon.com)
生物谷推薦的英文摘要
Multidisciplinary Journal of Microbial Ecology doi:10.1038/ismej.2013.36
Miguel Valvano B.cenocepaciaThe unexpected discovery of a novel low-oxygen-activated locus for the anoxic persistence of Burkholderia cenocepacia.
Sass AM, Schmerk C, Agnoli K, Norville PJ, Eberl L, Valvano MA, Mahenthiralingam E.
Burkholderia cenocepacia is a Gram-negative aerobic bacterium that belongs to a group of opportunistic pathogens displaying diverse environmental and pathogenic lifestyles. B. cenocepacia is known for its ability to cause lung infections in people with cystic fibrosis and it possesses a large 8 Mb multireplicon genome encoding a wide array of pathogenicity and fitness genes. Transcriptomic profiling across nine growth conditions was performed to identify the global gene expression changes made when B. cenocepacia changes niches from an environmental lifestyle to infection. In comparison to exponential growth, the results demonstrated that B. cenocepacia changes expression of over one-quarter of its genome during conditions of growth arrest, stationary phase and surprisingly, under reduced oxygen concentrations (6% instead of 20.9% normal atmospheric conditions). Multiple virulence factors are upregulated during these growth arrest conditions. A unique discovery from the comparative expression analysis was the identification of a distinct, co-regulated 50-gene cluster that was significantly upregulated during growth under low oxygen conditions. This gene cluster was designated the low-oxygen-activated (lxa) locus and encodes six universal stress proteins and proteins predicted to be involved in metabolism, transport, electron transfer and regulation. Deletion of the lxa locus resulted in B. cenocepacia mutants with aerobic growth deficiencies in minimal medium and compromised viability after prolonged incubation in the absence of oxygen. In summary, transcriptomic profiling of B. cenocepacia revealed an unexpected ability of aerobic Burkholderia to persist in the absence of oxygen and identified the novel lxa locus as key determinant of this important ecophysiological trait.