The proton motive force determines<i>Escherichia coli</i>’s robustness to extracellular pH

Terradot, Guillaume; Krasnopeeva, Ekaterina; Swain, Peter S.; Pilizota, Teuta

doi:10.1101/2021.11.19.469321

“…Some studies highlighted the function of mitochondria in biosynthesis (Visser et al 1994 ) and lipid metabolism (Reiner et al 2006 ) and suggested that maintaining functional mitochondria in anaerobic conditions is an energy-costly process (Drgoň et al 1991 , Visser et al 1994 ). Moreover, recent reports allow us to speculate that maintenance of proton-motive force across cell membranes could be one of the factors leading to extra costs in anaerobic growth ((Malina et al 2021 , Terradot et al 2021 ), T. Pilizota, personal communication). Aerobically, the proton-motive force is generated by the electron transport chain in the mitochondrial inner membrane, and some of it is used for, e.g.…”

Section: Discussionmentioning

confidence: 99%

Elevated energy costs of biomass production in mitochondrial respiration-deficientSaccharomyces cerevisiae

Grigaitis

¹

,

Bogaard

²

,

Teusink

³

2023

FEMS Yeast Research

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Microbial growth requires energy for maintaining the existing cells and producing components for the new ones. Microbes therefore invest a considerable amount of their resources into proteins needed for energy harvesting. Growth in different environments is associated with different energy demands for growth of yeast Saccharomyces cerevisiae, although the cross-condition differences remain poorly characterized. Furthermore, a direct comparison of the energy costs for the biosynthesis of the new biomass across conditions is not feasible experimentally; computational models, on the contrary, allow comparing the optimal metabolic strategies and quantify the respective costs of energy and nutrients. Thus in this study, we used a resource allocation model of S. cerevisiae to compare the optimal metabolic strategies between different conditions. We found that S. cerevisiae with respiratory-impaired mitochondria required additional energetic investments for growth, while growth on amino acid-rich media was not affected. Amino acid supplementation in anaerobic conditions also was predicted to rescue the growth reduction in mitochondrial respiratory shuttle-deficient mutants of S. cerevisiae. Collectively, these results point to elevated costs of resolving the redox imbalance caused by de novo biosynthesis of amino acids in mitochondria. To sum up, our study provides an example of how resource allocation modeling can be used to address and suggest explanations to open questions in microbial physiology.

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“…Some studies highlighted the function of mitochondria in biosynthesis (Visser et al, 1994) and lipid metabolism (Reiner et al, 2006) and suggested that maintaining functional mitochondria in anaerobic conditions is an energy-costly process (Drgoň et al, 1991;Visser et al, 1994). Moreover, recent reports allow us to speculate that maintenance of proton-motive force across cell membranes could be one of the factors leading to extra costs in anaerobic growth ( (Malina et al, 2021;Terradot et al, 2021), T. Pilizota, personal communication). Aerobically, the proton-motive force is generated by the electron transport chain in the mitochondrial inner membrane, and some of it is used for, e.g.…”

Section: Discussionmentioning

confidence: 99%

Elevated energy costs of biomass production in mitochondrial-respiration deficientSaccharomyces cerevisiae

Grigaitis

¹

,

Bogaard

²

,

Teusink

³

2022

Preprint

1

0

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Microbial growth requires energy for maintaining the existing cells and producing components for the new ones. Microbes therefore invest a considerable amount of their resources into proteins needed for energy harvesting. Growth in different environments is associated with different energy demands for growth of yeast Saccharomyces cerevisiae, although the cross-condition differences remain poorly characterized. Furthermore, a direct comparison of the energy costs for the biosynthesis of the new biomass across conditions is not feasible experimentally; computational models, on the contrary, allow comparing the optimal metabolic strategies and quantify the respective costs of energy and nutrients. Thus in this study, we used a resource allocation model of S. cerevisiae to compare the optimal metabolic strategies between different conditions. We found that S. cerevisiae with respiratory-impaired mitochondria required additional energetic investments for growth, while growth on amino acid-rich media was not affected. Amino acid supplementation in anaerobic conditions also was predicted to rescue the growth reduction in mitochondrial respiratory shuttle-deficient mutants of S. cerevisiae. Collectively, these results point to elevated costs of resolving the redox imbalance caused by de novo biosynthesis of amino acids in mitochondria. To sum up, our study provides an example of how resource allocation modeling can be used to address and suggest explanations to open questions in microbial physiology.

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“…give rise to new generation of antibiotic-tolerant persister cells [4]. Efflux pumps, which cause multidrug resistance, need PMF to energize its pumping of antibiotics from cells [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Antibiotics, Efflux, and pH

Hillman¹

2023

Archives of Proteomics and Bioinformatics

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Bacterial metabolism affects the effectiveness of antibiotics. Bacterial metabolism is linked to the ability of an antibiotic to be bactericidal or bacteriostatic because a bacterium can metabolize carbohydrates that affect its pH and its ability to use the proton motive force (PMF). When the pH is low, there is more availability of protons that can help to power the proton motive force needed for the efflux of antibiotics. Antibiotics increase the internal pH of a bacterial cell, but when the external pH is low or acidic, the lethality of the antibiotics dwindles. Adding an efflux inhibitor (EI) can block the efflux of antibiotics; however, the pH also affects the effectiveness of the efflux inhibitor. At a low pH the efflux inhibitor cannot block the efflux of antibiotics. This is important for the effectiveness of EIs to block efflux in acidic bacterial environments such as in the stomach or in the small intestines where the pH is highly acidic and low. However, in the colon the pH is highly alkaline and higher leading to a lesser availability of protons, in which the bacterial cells must rely on carbohydrate metabolism to expel any noxious agent such as an antibiotic via the ATP activation of the ABC transporter. As a consequence, for an efflux inhibitor to be effective the pH and the metabolism of carbohydrates to power the ABC transporter must be considered in the design of potential efflux inhibitors. This commentary will offer support for the arguments made in the article, Reducing bacterial antibiotic resistance by targeting bacterial metabolic pathways and disrupting RND efflux pump activity, by presenting the results of experiments that prove the gene inhibition of the AcrAB-TolC subunits of AcrB and TolC as a potent and effective EI design.

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The proton motive force determinesEscherichia coli’s robustness to extracellular pH

Cited by 9 publications

References 84 publications

Elevated energy costs of biomass production in mitochondrial respiration-deficientSaccharomyces cerevisiae

Elevated energy costs of biomass production in mitochondrial respiration-deficientSaccharomyces cerevisiae

Elevated energy costs of biomass production in mitochondrial-respiration deficientSaccharomyces cerevisiae

Antibiotics, Efflux, and pH

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