西方大学最新研究发现了存在于细菌间的一种新的通讯手段,通过这种手段洋葱伯克霍尔德菌(B.cenocepacia)可以联合抵御抗生素的作用。洋葱伯克霍尔德菌是一种条件致病菌,也是医院感染的重要病原菌之一。它可以导致感染者囊肿性纤维化(CF)或者免疫系统受损。
洋葱伯克霍尔德菌对多种抗菌药具有天然的耐药性
Miguel Valvano博士称,在细菌种群间,那些对抗生素抗性较强的细菌将产生的耐药小分子与另外一些对抗生素抗性较弱的细菌分享,以使其对抗生素的耐性更强。这些小分子大都是一些经过修饰的氨基酸,它们不但可以保护那些较为敏感的洋葱伯克霍尔德菌,甚至还可以保护较为常见的CF病原体,例如铜绿假单胞菌和大肠杆菌等。
“这项研究揭示了一种新的耐药机制,细菌间通过小分子进行化学信号传递来共同抵御抗生素的作用。这为以后药物研发提供了新的思路,研发抗生素药物应当尽量避免其受这些化学小分子的作用以便抗生素能有效发挥药效。”Belfast女王大学的教授兼系主任Valvano教授说道。
El-Halfaw博士兴奋地说:“除了有限的几类细菌除外,几乎所有的细菌都可以利用和产生这些化学小分子,所以我们可以将这种小分子视作一种细菌间进行通讯的语言。另外,洋葱伯克霍尔德菌对抵御抗生素的药性还有另外一种更高级的方式,它们可以通过释放小分子蛋白与抗生素结合来降低抗生素的有效性。”下一步就是找到解决方法来抑制这种现象的产生。
这项研究是由西方大学负责的,由加拿大囊肿性纤维化基金会和居里夫人基金会资助的。(生物谷 Bioon.com)
生物谷推荐的英文摘要
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.