Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Richardson Road, NE2 4AX Newcastle upon Tyne, UK.
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Richardson Road, NE2 4AX Newcastle upon Tyne, UK; Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
Cell. 2014 Apr 24;157(3):539-48. doi: 10.1016/j.cell.2014.02.050.
All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent technological advances in microfluidics and reporter genes have improved this scenario. Here, we summarize recent progress in the field, revealing the ubiquitous bacterial stress alarmone ppGpp as an emerging central regulator of multidrug tolerance and persistence, both in stochastically and environmentally induced persistence. In several different organisms, toxin-antitoxin modules function as effectors of ppGpp-induced persistence.
所有细菌都会形成持留细胞,这些细胞对多种药物具有耐受性,因此能够在抗生素治疗中存活下来。由于在生长中的细菌培养物中持留细胞的频率较低,以及潜在的分子机制复杂,因此该现象一直难以研究。然而,微流控和报告基因等新技术的发展改善了这一情况。在这里,我们总结了该领域的最新进展,揭示了普遍存在的细菌应激感应核苷酸 ppGpp 作为一种新兴的多药耐受性和持留性的中央调节剂,无论是在随机诱导还是环境诱导的持留性中都是如此。在几种不同的生物体中,毒素-抗毒素模块作为 ppGpp 诱导持留的效应物发挥作用。