Howard Hughes Medical Institute, Boston University, Boston, MA 02215, USA.
Cell Host Microbe. 2013 Jun 12;13(6):632-42. doi: 10.1016/j.chom.2013.05.009.
Microbial drug persistence is a widespread phenomenon in which a subpopulation of microorganisms is able to survive antimicrobial treatment without acquiring resistance-conferring genetic changes. Microbial persisters can cause recurrent or intractable infections, and, like resistant mutants, they carry an increasing clinical burden. In contrast to heritable drug resistance, however, the biology of persistence is only beginning to be unraveled. Persisters have traditionally been thought of as metabolically dormant, nondividing cells. As discussed in this review, increasing evidence suggests that persistence is in fact an actively maintained state, triggered and enabled by a network of intracellular stress responses that can accelerate processes of adaptive evolution. Beyond shedding light on the basis of persistence, these findings raise the possibility that persisters behave as an evolutionary reservoir from which resistant organisms can emerge. As persistence and its consequences come into clearer focus, so too does the need for clinically useful persister-eradication strategies.
微生物药物持久性是一种广泛存在的现象，其中一部分微生物能够在没有获得赋予耐药性的遗传变化的情况下，在抗微生物治疗中存活下来。微生物持久存在者会导致反复或难治性感染，并且与耐药突变体一样，它们带来的临床负担越来越大。然而，与可遗传的耐药性不同，持久性的生物学机制才刚刚开始被揭示。持久存在者传统上被认为是代谢休眠、不分裂的细胞。正如本文综述所讨论的那样，越来越多的证据表明，持久性实际上是一种被积极维持的状态，由一系列细胞内应激反应网络触发和支持，这些反应网络可以加速适应性进化的过程。除了阐明持久性的基础之外，这些发现还提出了一种可能性，即持久存在者表现为一种进化储备库，耐药生物可以从中出现。随着持久性及其后果变得更加清晰，也需要临床有用的持久存在者消除策略。
