Antibiotics as signal molecules.

Antibiotics as signal molecules.
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抗生素作为信号分子。

DOI:
10.1021/cr2000509
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发表时间:
2011-09-14
期刊:
影响因子:
62.1
通讯作者:
Kolter, Roberto
Kolter, Roberto
中科院分区:
化学1区
文献类型:
--
作者:
Romero, Diego;Traxler, Matthew F.;Lopez, Daniel;Kolter, Roberto

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在过去的五十年里,抗生素的过度使用导致了病原菌的广泛耐药性。这种耐药性,再加上新疗法的设计进展缓慢,导致许多曾经容易治愈的疾病的治疗出现危机。人们已经投入了很大的努力来开发有效靶向微生物生命的基本特征的新化合物,但对于大多数人来说,只有它们的生长抑制作用得到了广泛的研究。低浓度的抗菌剂如何影响细菌的存活,最重要的是,这些分子在亚抑制浓度(SICs)下是否具有其他功能是一个悬而未决的问题。关于许多重要的人类病原体对抗生素的SIC的全局转录组响应的开创性研究已经证明,这些分子可以影响与毒力、定殖、运动性、应激反应和/或生物膜形成相关的基因的表达。进一步的研究表明,这些影响中的一些是由于干扰细菌细胞间的细胞通讯。这一观察结果促使人们认为抗生素实际上可能在自然环境中充当信号分子,促进微生物群落内的种内或种间相互作用。在这篇综述中,我们强调了各种临床相关的抗菌剂和其他天然产物对细菌发育程序的影响的例子,重点是生物膜的形成。如何利用这些知识来改善目前抗生素的使用,以及如何开发针对替代微生物过程的新疗法也将被讨论。
Over the last five decades, the overuse of antibiotics has led to widespread resistance in pathogenic bacteria. This resistance, combined with slow progress in designing new therapeutics, has prompted a crisis in the treatment of many once easily curable diseases. Great effort has been put into developing new compounds that effectively target essential features of microbial life, but for the majority, only their growth inhibitory effects have been extensively studied. How low concentrations of antimicrobials affect bacterial survival and, most importantly, whether or not the molecules might have other functions at subinhibitory concentrations (SICs) are outstanding questions. Pioneering studies on the global transcriptome response of many important human pathogens to SICs of antibiotics have demonstrated that these molecules can affect the expression of genes related to virulence, colonization, motility, stress response, and/or biofilm formation. Further research has shown that some of these effects result from interference with bacterial cellÀcell communication. This observation has prompted the idea that antibiotics might actually act as signal molecules in natural environments, facilitating intra-or interspecies interactions within microbial communities. In this review, we highlight examples of the effect of diverse clinically relevant antimicrobials and other natural products on bacterial developmental programs, with an emphasis on biofilm formation. How this knowledge can be used to improve the current use of antibiotics and how new therapies that target alternative microbial processes might be developed will also be discussed.
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