Butler George, Bos Julia, Austin Robert H, Amend Sarah R, Pienta Kenneth J
Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Institut Pasteur, Université de Paris Cité, CNRS UMR 3525, Unité Plasticité du Génome Bactérien, Paris, France.
R Soc Open Sci. 2023 Aug 9;10(8):230338. doi: 10.1098/rsos.230338. eCollection 2023 Aug.
The evolution of antibiotic resistance is a fundamental problem in disease management but is rarely quantified on a single-cell level owing to challenges associated with capturing the spatial and temporal variation across a population. To evaluate cell biological phenotypic responses, we tracked the single-cell dynamics of filamentous bacteria through time in response to ciprofloxacin antibiotic stress. We measured the degree of phenotypic variation in nucleoid length and the accumulation of protein damage under ciprofloxacin antibiotic and quantified the impact on bacterial survival. Increased survival was correlated with increased nucleoid length and the variation in this response was inversely correlated with antibiotic concentration. Survival time was also increased through clearance of misfolded proteins, an unexpected mechanism of stress relief deployed by the filamentous bacteria. Our results reveal a diverse range of survival tactics employed by bacteria in response to ciprofloxacin and suggest potential evolutionary routes to resistance.
抗生素耐药性的演变是疾病管理中的一个基本问题，但由于在捕捉群体中的时空变化方面存在挑战，很少在单细胞水平上进行量化。为了评估细胞生物学表型反应，我们追踪了丝状细菌在环丙沙星抗生素应激下随时间的单细胞动态。我们测量了环丙沙星抗生素作用下类核长度的表型变化程度和蛋白质损伤的积累，并量化了对细菌存活的影响。存活率的提高与类核长度的增加相关，而这种反应的变化与抗生素浓度呈负相关。丝状细菌通过清除错误折叠的蛋白质也增加了存活时间，这是一种意想不到的应激缓解机制。我们的结果揭示了细菌应对环丙沙星所采用的多种存活策略，并提出了潜在的耐药进化途径。
