Lemma Annabel S, Soto-Echevarria Nashaly, Brynildsen Mark P
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Microorganisms. 2022 Jan 26;10(2):286. doi: 10.3390/microorganisms10020286.
When faced with nutritional deprivation, bacteria undergo a range of metabolic, regulatory, and biosynthetic changes. Those adjustments, which can be specific or independent of the missing nutrient, often alter bacterial tolerance to antibiotics. Here, using fluoroquinolones, we quantified persister levels in cultures experiencing starvation from a lack of carbon (C), nitrogen (N), phosphorous (P), or magnesium (Mg). Interestingly, persister levels varied significantly based on the type of starvation as well as fluoroquinolone used with N-starved populations exhibiting the highest persistence to levofloxacin, and P-starved populations exhibiting the highest persistence to moxifloxacin. However, regardless of the type of starvation or fluoroquinolone used, DNA repair was required by persisters, with ∆ and ∆ uniformly exhibiting the lowest persistence of the mutants assayed. These results suggest that while the type of starvation and fluoroquinolone will modulate the level of persistence, the importance of homologous recombination is consistently observed, which provides further support for efforts to target homologous recombination for anti-persister purposes.
当面临营养剥夺时，细菌会经历一系列代谢、调节和生物合成变化。这些调整可能是特定于缺失营养素的，也可能与之无关，它们常常会改变细菌对抗生素的耐受性。在此，我们使用氟喹诺酮类药物，对因缺乏碳（C）、氮（N）、磷（P）或镁（Mg）而处于饥饿状态培养物中的持留菌水平进行了量化。有趣的是，持留菌水平会因饥饿类型以及所用氟喹诺酮类药物的不同而有显著差异，氮饥饿群体对左氧氟沙星的耐受性最高，磷饥饿群体对莫西沙星的耐受性最高。然而，无论饥饿类型或所用氟喹诺酮类药物如何，持留菌都需要DNA修复，在所检测的突变体中，Δ和Δ始终表现出最低的耐受性。这些结果表明，虽然饥饿类型和氟喹诺酮类药物会调节耐受性水平，但同源重组的重要性始终存在，这为以同源重组为靶点实现抗持留菌目的所做的努力提供了进一步支持。
