Dataset Information

Metformin Alters the Chemotaxis and Flagellar Motility of Escherichia coli.

ABSTRACT: Metformin is a biguanide molecule that is widely prescribed to treat type 2 diabetes and metabolic syndrome. Although it is known that metformin promotes the lifespan by altering intestinal microorganism metabolism, how metformin influences and alters the physiological behavior of microorganisms remains unclear. Here we studied the effect of metformin on the behavior alterations of the model organism Escherichia coli (E. coli), including changes in chemotaxis and flagellar motility that plays an important role in bacterial life. It was found that metformin was sensed as a repellent to E. coli by tsr chemoreceptors. Moreover, we investigated the chemotactic response of E. coli cultured with metformin to two typical attractants, glucose and α-methyl-DL-aspartate (MeAsp), finding that metformin prolonged the chemotactic recovery time to the attractants, followed by the recovery time increasing with the concentration of stimulus. Metformin also inhibited the flagellar motility of E. coli including the flagellar motor rotation and cell swimming. The inhibition was due to the reduction of torque generated by the flagellar motor. Our discovery that metformin alters the behavior of chemotaxis and flagellar motility of E. coli could provide potential implications for the effect of metformin on other microorganisms.

SUBMITTER: Ye Y

PROVIDER: S-EPMC8787215 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Metformin Alters the Chemotaxis and Flagellar Motility of Escherichia coli.

Ye Yingxiang Y Jiang Panmei P Huang Chengyun C Li Jingyun J Chen Juan J Wang Lu L Lin Yan Y Wang Fangbin F Liu Jian J

Frontiers in microbiology 20220111

Metformin is a biguanide molecule that is widely prescribed to treat type 2 diabetes and metabolic syndrome. Although it is known that metformin promotes the lifespan by altering intestinal microorganism metabolism, how metformin influences and alters the physiological behavior of microorganisms remains unclear. Here we studied the effect of metformin on the behavior alterations of the model organism Escherichia coli (E. coli), including changes in chemotaxis and flagellar motility ...[more]

PMID: 35087494

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Project description:Gene expression profiles of Escherichia coli K-12 W3110 were compared as a function of steady-state external pH. Cultures were grown with aeration to an optical density at 600 nm of 0.3 in potassium-modified Luria-Bertani medium buffered at pH 5.0, 7.0, and 8.7. For each of the three pH conditions, cDNA from RNA of five independent cultures was hybridized to Affymetrix E. coli arrays. Analysis of variance with a significance level of 0.001 resulted in 98% power to detect genes showing a twofold difference in expression. Normalized expression indices were calculated for each gene and intergenic region (IG). Differential expression among the three pH classes was observed for 763 genes and 353 IGs. Hierarchical clustering yielded six well-defined clusters of pH profiles, designated Acid High (highest expression at pH 5.0), Acid Low (lowest expression at pH 5.0), Base High (highest at pH 8.7), Base Low (lowest at pH 8.7), Neutral High (highest at pH 7.0, lower in acid or base), and Neutral Low (lowest at pH 7.0, higher at both pH extremes). Flagellar and chemotaxis genes were repressed at pH 8.7 (Base Low cluster), where the cell's transmembrane proton potential is diminished by the maintenance of an inverted pH gradient. High pH also repressed the proton pumps cytochrome o (cyo) and NADH dehydrogenases I and II. By contrast, the proton-importing ATP synthase F1Fo and the microaerophilic cytochrome d (cyd), which minimizes proton export, were induced at pH 8.7. These observations are consistent with a model in which high pH represses synthesis of flagella, which expend proton motive force, while stepping up electron transport and ATPase components that keep protons inside the cell. Acid-induced genes, on the other hand, were coinduced by conditions associated with increased metabolic rate, such as oxidative stress. All six pH-dependent clusters included envelope and periplasmic proteins, which directly experience external pH. Overall, this study showed that (i) low pH accelerates acid consumption and proton export, while coinducing oxidative stress and heat shock regulons; (ii) high pH accelerates proton import, while repressing the energy-expensive flagellar and chemotaxis regulons; and (iii) pH differentially regulates a large number of periplasmic and envelope proteins. Keywords: Steady State

Project description:Gene expression profiles of Escherichia coli K-12 W3110 were compared as a function of steady-state external pH. Cultures were grown to an optical density at 600 nm of 0.3 in potassium-modified Luria-Bertani medium buffered at pH 5.0, 7.0, and 8.7. For each of the three pH conditions, cDNA from RNA of five independent cultures was hybridized to Affymetrix E. coli arrays. Analysis of variance with an alpha level of 0.001 resulted in 98% power to detect genes showing a twofold difference in expression. Normalized expression indices were calculated for each gene and intergenic region (IG). Differential expression among the three pH classes was observed for 763 genes and 353 IGs. Hierarchical clustering yielded six well-defined clusters of pH profiles, designated Acid High (highest expression at pH 5.0), Acid Low (lowest expression at pH 5.0), Base High (highest at pH 8.7), Base Low (lowest at pH 8.7), Neutral High (highest at pH 7.0, lower in acid or base), and Neutral Low (lowest at pH 7.0, higher at both pH extremes). Flagellar and chemotaxis genes were repressed at pH 8.7 (Base Low cluster), where the cell's transmembrane proton potential is diminished by the maintenance of an inverted pH gradient. High pH also repressed the proton pumps cytochrome o (cyo) and NADH dehydrogenases I and II. By contrast, the proton-importing ATP synthase F1Fo and the microaerophilic cytochrome d (cyd), which minimizes proton export, were induced at pH 8.7. These observations are consistent with a model in which high pH represses synthesis of flagella, which expend proton motive force, while stepping up electron transport and ATPase components that keep protons inside the cell. Acid-induced genes, on the other hand, were coinduced by conditions associated with increased metabolic rate, such as oxidative stress. All six pH-dependent clusters included envelope and periplasmic proteins, which directly experience external pH. Overall, this study showed that (i) low pH accelerates acid consumption and proton export, while coinducing oxidative stress and heat shock regulons; (ii) high pH accelerates proton import, while repressing the energy-expensive flagellar and chemotaxis regulons; and (iii) pH differentially regulates a large number of periplasmic and envelope proteins.

Dataset Information

Metformin Alters the Chemotaxis and Flagellar Motility of Escherichia coli.

Publications

Metformin Alters the Chemotaxis and Flagellar Motility of <i>Escherichia coli</i>.

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