Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas Madrid, Spain.
Front Microbiol. 2013 Apr 30;4:103. doi: 10.3389/fmicb.2013.00103. eCollection 2013.
Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.
近年来，固有耐药细菌已成为一个重要的健康问题。这些细菌物种，其中一些具有环境起源，对几种药物天然具有低水平的敏感性。有人提出，固有耐药性主要是由于细胞包膜的通透性差、多药外排泵的活性或缺乏针对特定药物家族的适当靶标所致。然而，最近发表的文章表明，给定细菌物种对抗生素敏感性的特征表型取决于几个要素的协同作用，这被称为固有耐药组。这些决定因素不仅包括经典的耐药基因。其他一些与细菌基本代谢过程有关的元素对于细菌病原体的固有耐药性也很重要。在本综述中，我们分析了关于大肠杆菌和铜绿假单胞菌固有耐药组的最新研究。我们还介绍了细菌代谢全局调节剂（如铜绿假单胞菌中的 Crc）在调节细菌对抗生素敏感性方面可能发挥的作用。最后，我们讨论了在固有耐药组中寻找抑制剂的可能性，以期提高目前临床应用药物的活性。
