Proteolytic Queues at ClpXP Increase Antibiotic Tolerance.,ACS Synthetic Biology

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Proteolytic Queues at ClpXP Increase Antibiotic Tolerance.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-01-03 , DOI: 10.1021/acssynbio.9b00358
Heather S Deter ₁ , Alawiah H Abualrahi ₁ , Prajakta Jadhav ₁ , Elise K Schweer ₁ , Curtis T Ogle , Nicholas C Butzin ₁

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Antibiotic tolerance is a widespread phenomenon that renders antibiotic treatments less effective and facilitates antibiotic resistance. Here we explore the role of proteases in antibiotic tolerance, short-term population survival of antibiotics, using queueing theory (i.e., the study of waiting lines), computational models, and a synthetic biology approach. Proteases are key cellular components that degrade proteins and play an important role in a multidrug tolerant subpopulation of cells, called persisters. We found that queueing at the protease ClpXP increases antibiotic tolerance ∼80 and ∼60 fold in an E. coli population treated with ampicillin and ciprofloxacin, respectively. There does not appear to be an effect on antibiotic persistence, which we distinguish from tolerance based on population decay. These results demonstrate that proteolytic queueing is a practical method to probe proteolytic activity in bacterial tolerance and related genes, while limiting the unintended consequences frequently caused by gene knockout and overexpression.

中文翻译：

ClpXP 的蛋白水解队列可提高抗生素耐受性。

抗生素耐受是一种普遍现象，它会降低抗生素治疗的效果并促进抗生素耐药性。在这里，我们利用排队理论（即排队的研究）、计算模型和合成生物学方法，探讨蛋白酶在抗生素耐受性、抗生素短期群体生存中的作用。蛋白酶是降解蛋白质的关键细胞成分，并在多药耐受细胞亚群（称为持久细胞）中发挥重要作用。我们发现，在用氨苄西林和环丙沙星处理的大肠杆菌群体中，在蛋白酶 ClpXP 处排队分别使抗生素耐受性增加约 80 倍和约 60 倍。抗生素的持久性似乎没有受到影响，我们将其与基于种群衰退的耐受性区分开来。这些结果表明，蛋白水解排队是探测细菌耐受性和相关基因中蛋白水解活性的实用方法，同时限制了基因敲除和过度表达经常引起的意外后果。

更新日期：2020-01-04

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