Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
FEMS Microbiol Rev. 2011 Sep;35(5):768-89. doi: 10.1111/j.1574-6976.2011.00282.x. Epub 2011 Jun 28.
It is generally assumed that antibiotics and resistance determinants are the task forces of a biological warfare in which each resistance determinant counteracts the activity of a specific antibiotic. According to this view, antibiotic resistance might be considered as a specific response to an injury, not necessarily linked to bacterial metabolism, except for the burden that the acquisition of resistance might impose on the bacteria (fitness costs). Nevertheless, it is known that changes in bacterial metabolism, such as those associated with dormancy or biofilm formation, modulate bacterial susceptibility to antibiotics (phenotypic resistance), indicating that there exists a linkage between bacterial metabolism and antibiotic resistance. The analyses of the intrinsic resistomes of bacterial pathogens also demonstrate that the building up of intrinsic resistance requires the concerted action of many elements, several of which play a relevant role in the bacterial metabolism. In this article, we will review the current knowledge on the linkage between bacterial metabolism and antibiotic resistance and will discuss the role of global metabolic regulators such as Crc in bacterial susceptibility to antibiotics. Given that growing into the human host requires a metabolic adaptation, we will discuss whether this adaptation might trigger resistance even in the absence of selective pressure by antibiotics.
人们普遍认为，抗生素和耐药决定因素是生物战的先锋队，每个耐药决定因素都能对抗特定抗生素的活性。根据这种观点，抗生素耐药性可以被视为对损伤的一种特定反应，不一定与细菌代谢有关，除非获得耐药性会给细菌带来负担（适应度成本）。然而，众所周知，细菌代谢的变化，如与休眠或生物膜形成相关的变化，会调节细菌对抗生素的敏感性（表型耐药），这表明细菌代谢和抗生素耐药性之间存在联系。对细菌病原体固有耐药组的分析也表明，固有耐药的建立需要许多因素的协同作用，其中有几个因素在细菌代谢中起着重要作用。在本文中，我们将回顾细菌代谢和抗生素耐药性之间联系的最新知识，并讨论 Crc 等全局代谢调节剂在细菌对抗生素敏感性中的作用。鉴于在进入人体宿主时需要进行代谢适应，我们将讨论即使没有抗生素的选择压力，这种适应是否会引发耐药性。
