Roch Elsa, Ducrocq Jérémie, Jacquier Nicolas
School of Biology, University of Lausanne, Lausanne, 1015, Switzerland.
Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, 1011, Switzerland.
BMC Microbiol. 2025 Aug 8;25(1):488. doi: 10.1186/s12866-025-04210-1.
Antibiotic resistance is a growing threat for modern medicine, making treatment of infectious diseases increasingly tedious. However, even non-resistant bacteria can survive treatment and cause recurrent infections. This phenomenon is often due to non-proliferating bacteria able to survive the treatment and to resume infection afterwards, also called recalcitrant bacteria. Bacterial recalcitrance, which encompasses tolerance and persistence, is defined by increased survival of bacteria in the presence of antimicrobial agents. In contrast to resistance, the mechanisms underlying recalcitrance are only partially understood. In this review, we summarise the recent advances in the understanding of recalcitrance, its detection, as well as anti-recalcitrance therapies that have been developed. Recalcitrance is thought to be caused by a reduction of bacterial metabolism, mostly driven by stringent and SOS responses, leading to bacterial dormancy. These dormant bacteria escape the action of many antibiotics, preventing the complete resolution of infection. However, strategies have been proposed to tackle recalcitrance. Recalcitrant bacteria are susceptible to drugs whose action is independent of metabolic activity, such as membrane-targeting compounds. Inhibitors blocking the entry of bacteria into dormancy or locking bacteria in a permanent state of dormancy could help avoid recurrence of the infection. Dormant bacteria could also be forced to resume growth through supply of nutrients or signalling molecules. A phage specifically targeting dormant bacteria was recently described and may be an important tool to fight bacterial recalcitrance. Recalcitrance has been neglected for a long time, being in the shadow of resistance. However, both phenomena need to be further investigated in the future to develop a complete array of antibacterial agents that will allow to permanently eradicate all types of bacterial infections.
抗生素耐药性对现代医学构成了日益严重的威胁，使得传染病的治疗变得越来越棘手。然而，即使是非耐药细菌也能在治疗后存活并导致反复感染。这种现象通常是由于非增殖性细菌能够在治疗中存活下来，并在之后重新引发感染，这类细菌也被称为顽固性细菌。细菌顽固性包括耐受性和持续性，其定义为细菌在抗菌剂存在下存活率增加。与耐药性不同，顽固性背后的机制仅得到部分理解。在本综述中，我们总结了在理解顽固性、其检测方法以及已开发的抗顽固性疗法方面的最新进展。顽固性被认为是由细菌代谢降低引起的，主要由严格反应和SOS反应驱动，导致细菌进入休眠状态。这些休眠细菌逃避了许多抗生素的作用，从而阻止了感染的完全消除。然而，已经提出了应对顽固性的策略。顽固性细菌对其作用不依赖于代谢活性的药物敏感，例如靶向膜的化合物。阻断细菌进入休眠状态或使细菌锁定在永久休眠状态的抑制剂可能有助于避免感染复发。也可以通过提供营养物质或信号分子来迫使休眠细菌恢复生长。最近描述了一种专门靶向休眠细菌的噬菌体，它可能是对抗细菌顽固性的一种重要工具。长期以来，顽固性一直被忽视，处于耐药性的阴影之下。然而，未来这两种现象都需要进一步研究，以开发出一套完整的抗菌剂，从而能够永久根除所有类型的细菌感染。
