Abstract
Persister cells (persisters) are transiently tolerant to antibiotics and usually constitute a small part of bacterial populations. Persisters remain dormant but are able to re-grow after antibiotic treatment. In this study we found that the frequency of persisters correlated to the level of protein aggregates accumulated in E. coli stationary-phase cultures. When 3-(N-morpholino) propanesulfonic acid or an osmolyte (trehalose, betaine, glycerol or glucose) were added to the growth medium at low concentrations, proteins were prevented from aggregation and persister formation was inhibited. On the other hand, acetate or high concentrations of osmolytes enhanced protein aggregation and the generation of persisters. We demonstrated that in the E. coli stationary-phase cultures supplemented with MOPS or a selected osmolyte, the level of protein aggregates and persister frequency were not correlated with such physiological parameters as the extent of protein oxidation, culturability, ATP level or membrane integrity. The results described here may help to understand the mechanisms underlying persister formation.
Highlights
All genetically homogeneous bacterial populations produce a small number of dormant cells that survive prolonged exposure to high concentrations of antibiotics [1,2]
Since persistence can be regarded as a symptom of bacterial aging [24], we examined the influence of MOPS and osmolytes on the physiological parameters that are known to change in aging cultures: the extent of protein oxidation, culturability, the level of ATP and membrane stability [25,26,27]
The Frequency of Persisters is Associated with the Level of Protein Aggregates but not with the Amount of Oxidized Proteins Accumulated in Stationary-phase E. coli Cultures
Summary
All genetically homogeneous bacterial populations produce a small number of dormant cells that survive prolonged exposure to high concentrations of antibiotics [1,2]. These multidrug- tolerant persister cells are transient phenotypic variants of wild type cells, which become sensitive to antibiotics upon re-growth. Numerous studies indicate that toxin-antitoxin modules are required for persistence in E. coli. Analysis of E. coli transcriptomes revealed that other toxin-antitoxin (TA) genes (dinJ/yafQ, yefM, relBE, mazEF, ygiUT) belong to the group of nearly 300–420 genes upregulated in persisters [5,6]. The expression of stress genes suggests that persister formation is a survival strategy, but on the basis of these results it is difficult to explain antibiotic tolerance
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