Physiological and regulatory convergence between osmotic and nutrient stress responses in microbes

Brauer, Adrienne M; Shi, Handuo; Levin, Petra Anne; Huang, Kerwyn Casey

doi:10.1016/j.ceb.2023.102170

Cited by 11 publications

(11 citation statements)

References 55 publications

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“…It is therefore tempting to speculate that TisB is responsible for a controlled loss of potassium. In the case of plasmolysis induced by an osmotic shock, which is unrelated to tisB expression, cells respond rapidly to equilibrate the internal turgor pressure by importing ions such as potassium and synthesizing solutes, allowing them to return to homeostasis ( 59 ). In contrast, TisB-dependent cytoplasmic condensation remained stable for the entire duration of the treatment.…”

Section: Discussionmentioning

confidence: 99%

TisB protein is the single molecular determinant underlying multiple downstream effects of ofloxacin in Escherichia coli

Cayron,

Oms,

Schlechtweg

et al. 2024

Sci. Adv.

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Bactericidal antibiotics can cause metabolic perturbations that contribute to antibiotic-induced lethality. The molecular mechanism underlying these downstream effects remains unknown. Here, we show that ofloxacin, a fluoroquinolone that poisons DNA gyrase, induces a cascade of metabolic changes that are dependent on an active SOS response. We identified the SOS-regulated TisB protein as the unique molecular determinant responsible for cytoplasmic condensation, proton motive force dissipation, loss of pH homeostasis, and H 2 O 2 accumulation in Escherichia coli cells treated with high doses of ofloxacin. However, TisB is not required for high doses of ofloxacin to interfere with the function of DNA gyrase or the resulting rapid inhibition of DNA replication and lethal DNA damage. Overall, the study sheds light on the molecular mechanisms by which ofloxacin affects bacterial cells and highlights the role of the TisB protein in mediating these effects.

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Section: Discussionmentioning

confidence: 99%

TisB protein is the single molecular determinant underlying multiple downstream effects of ofloxacin in Escherichia coli

Cayron,

Oms,

Schlechtweg

et al. 2024

Sci. Adv.

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show abstract

“…Instead, primary drug-target interactions perturb various metabolic pathways to induce an array of downstream effects, which can cause damage to both DNA and proteins [22,[32][33][34][35]. To combat such damage, bacteria can induce both a nonspecific and specific stress response in which many similar proteins are upregulated in response to nutrient, antibiotic, or osmotic stress [17,34,36,37]. Bactericide-induced damage can be repaired by such proteins, e.g.…”

Section: A Resource Allocation Theory Of Cellular Stress Response In ...mentioning

confidence: 99%

“…Cells exhibit a general stress response which is induced in response to cellular damage, and is mediated by various signaling molecules and transcription factors including ppGpp and RpoS [1,36,37,42,43]. Thus, f S is indirectly activated by U, and we model its dependence by a simple sigmoidal function,…”

Section: A Resource Allocation Theory Of Cellular Stress Response In ...mentioning

confidence: 99%

Gene expression tradeoffs determine bacterial survival and adaptation to antibiotic stress

Kratz,

Banerjee

2024

Preprint

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To optimize their fitness, cells face the crucial task of efficiently responding to various stresses. This ne- cessitates striking a balance between conserving resources for survival and allocating resources for growth and division. The fundamental principles governing these tradeoffs is an outstanding challenge in the physics of living systems. In this study, we introduce a coarse-grained theoretical framework for bacterial physiology that establishes a connection between the physiological state of cells and their survival outcomes in dynamic environments, particularly in the context of antibiotic exposure. Predicting bacterial survival responses to varying antibiotic doses proves challenging due to the profound influence of the physiological state on critical parameters, such as the Minimum Inhibitory Concentration (MIC) and killing rates, even within an isogenic cell population. Our proposed theoretical model bridges the gap by linking extracellular antibiotic concentration and nutrient quality to intracellular damage accumulation and gene expression. This framework allows us to predict and explain the control of cellular growth rate, death rate, MIC and survival fraction in a wide range of time-varying environments. Surprisingly, our model reveals that cell death is rarely due to antibiotic levels being above the maximum physiological limit, but instead survival is limited by the inability to alter gene expression sufficiently quickly to transition to a less susceptible physiological state. Moreover, bacteria tend to overexpress stress response genes at the expense of reduced growth, conferring greater protection against further antibiotic exposure. This strategy is in contrast to those employed in different nutrient environments, in which bacteria allocate resources to maximize growth rate. This highlights an important tradeoff between the cellular capacity for growth and the ability to survive antibiotic exposure.

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“…Given that pyoverdin accumulation appears connected to cytoplasmic shrinkage, it seems reasonable to assume that other molecules may similarly accumulate in the periplasm in response to division arrest signals, which both change size and shape of cellular compartments. Indeed, accumulation of products related to nutrient stress is one possible function of the bacterial periplasm, with roles analogous to vacuoles in eukaryotes [50].…”

Section: Contained Within Cells Displaying a Homogeneous Distribution...mentioning

confidence: 99%

Polar accumulation of pyoverdin and exit from stationary phase

Moreno-Fenoll

Ardré

Rainey

2021

Preprint

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Pyoverdin is a water-soluble metal-chelator synthesized by members of the genus Pseudomonas and used for the acquisition of insoluble ferric iron. Although freely diffusible in aqueous environments, preferential dissemination of pyoverdin among adjacent cells, fine-tuning of intracellular siderophore concentrations, and fitness advantages to pyoverdin-producing versus nonproducing cells, indicate control of location and release. Here, using time-lapse fluorescence microscopy to track single cells in growing microcolonies of Pseudomonas fluorescens SBW25, we show accumulation of pyoverdin at cell poles. Accumulation is induced by arrest of cell division, is achieved by cross-feeding in pyoverdin-nonproducing mutants, is independent of cell shape, and is reversible. Furthermore, it occurs in multi-species communities. Analysis of the performance of pyoverdin-producing and nonproducing cells under conditions promoting polar localization shows an advantage to accumulation on resumption of growth after stress. While the genetic basis of polarization remains unclear, evaluation of deletion mutants of pyoverdin transporters (opmQ, fpvA) establishes non-involvement of these candidate loci. Examination of pyoverdin polar accumulation in a model community and in a range of laboratory and natural species of Pseudomonas, including P. aeruginosa PAO1 and P. putida KT2440, confirms that the phenotype is characteristic of Pseudomonas.

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Physiological and regulatory convergence between osmotic and nutrient stress responses in microbes

Cited by 11 publications

References 55 publications

TisB protein is the single molecular determinant underlying multiple downstream effects of ofloxacin in Escherichia coli

TisB protein is the single molecular determinant underlying multiple downstream effects of ofloxacin in Escherichia coli

Gene expression tradeoffs determine bacterial survival and adaptation to antibiotic stress

Polar accumulation of pyoverdin and exit from stationary phase

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