Zinc effects on bacteria: insights from Escherichia coli by multi-omics approach

mSystems, Год журнала: 2023, Номер 8(6)

Опубликована: Окт. 31, 2023

A long-term exposure of bacteria to zinc oxide and nanoparticles leads major alterations in bacterial morphology physiology. These included biochemical physiological processes promoting the emergence strains with multi-drug resistance virulence traits. After removal pressure, phenotype reversed back original state; however, certain changes at genomic, transcriptomic, proteomic level remained. Why is this important? The extensive intensive use supplements animal feed effects intestinal microbiota livestock may negatively impact health animals people. Therefore, it crucial understand monitor on microorganisms order adequately assess prevent potential risks.

Язык: Английский

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Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

eLife, Год журнала: 2024, Номер 13

Опубликована: Фев. 14, 2024

Aminoglycoside antibiotics target ribosomes and are effective against a wide range of bacteria. Here, we demonstrated that knockout strains related to energy metabolism in Escherichia coli showed increased tolerance aminoglycosides during the mid-exponential growth phase. Contrary expectations, these mutations did not reduce proton motive force or aminoglycoside uptake, as there were no significant changes metabolic indicators intracellular gentamicin levels between wild-type mutant strains. Our comprehensive proteomics analysis unveiled noteworthy upregulation proteins linked tricarboxylic acid (TCA) cycle phase, suggesting compensate for perturbation their by increasing TCA activity maintain membrane potential ATP levels. Furthermore, our pathway enrichment shed light on local network clusters displaying downregulation across all strains, which associated with both large small ribosomal binding proteins, ribosome biogenesis, translation factor activity, biosynthesis ribonucleoside monophosphates. These findings offer plausible explanation observed Altogether, this research provides valuable insights into mechanisms tolerance, paving way novel strategies combat such cells.

Язык: Английский

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Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

Опубликована: Июнь 5, 2024

Aminoglycoside antibiotics display broad-spectrum activity against Gram-negative and Gram-positive bacteria by targeting their ribosomes. Herein, we have demonstrated that energy metabolism plays a crucial role in aminoglycoside tolerance, as knockout strains associated with the tricarboxylic acid cycle (TCA) electron transport chain (ETC) exhibited increased tolerance to aminoglycosides mid-exponential growth phase of Escherichia coli cells. Given uptake relies on energy-driven electrochemical potential across cytoplasmic membrane, our initial expectation was these genetic perturbations would decrease proton motive force (PMF), subsequently affecting aminoglycosides. However, results did not corroborate this assumption. We found no consistent metabolic changes, ATP levels, pH variations, or membrane differences mutant compared wild type. Additionally, intracellular concentrations fluorophore-labeled gentamicin remained similar all strains. To uncover mechanism responsible for observed strains, employed untargeted mass spectrometry quantify proteins within mutants them wild-type counterparts. Our comprehensive analysis, which encompassed protein-protein association networks functional enrichment, unveiled noteworthy upregulation linked TCA during phase, suggesting compensate perturbation increasing maintain levels. Furthermore, pathway enrichment analysis shed light local network clusters displaying downregulation were both large small ribosomal binding proteins, ribosome biogenesis, translation factor activity, biosynthesis ribonucleoside monophosphates. These findings offer plausible explanation Altogether, research has mechanisms behind paving way novel strategies combat such

Язык: Английский

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An isogenic E. coli population gives rise to multiple persister phenotypes

International Journal of Antimicrobial Agents, Год журнала: 2024, Номер unknown, С. 107386 - 107386

Опубликована: Ноя. 1, 2024

Язык: Английский

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Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

eLife, Год журнала: 2024, Номер 13

Опубликована: Авг. 2, 2024

Aminoglycoside antibiotics target ribosomes and are effective against a wide range of bacteria. Here, we demonstrated that knockout strains related to energy metabolism in Escherichia coli showed increased tolerance aminoglycosides during the mid-exponential growth phase. Contrary expectations, these mutations did not reduce proton motive force or aminoglycoside uptake, as there were no significant changes metabolic indicators intracellular gentamicin levels between wild-type mutant strains. Our comprehensive proteomics analysis unveiled noteworthy upregulation proteins linked tricarboxylic acid (TCA) cycle phase, suggesting compensate for perturbation their by increasing TCA activity maintain membrane potential ATP levels. Furthermore, our pathway enrichment shed light on local network clusters displaying downregulation across all strains, which associated with both large small ribosomal binding proteins, ribosome biogenesis, translation factor activity, biosynthesis ribonucleoside monophosphates. These findings offer plausible explanation observed Altogether, this research provides valuable insights into mechanisms tolerance, paving way novel strategies combat such cells.

Язык: Английский

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Proton motive force and antibiotic tolerance in bacteria

Microbial Biotechnology, Год журнала: 2024, Номер 17(11)

Опубликована: Ноя. 1, 2024

Abstract Bacterial antibiotic tolerance is a decades‐old phenomenon in which bacterial sub‐population, commonly known as persisters, does not respond to antibiotics and remains viable upon prolonged antimicrobial treatment. Persisters are detectable populations of strains that antibiotic‐resistant be responsible for treatment failure the occurrence chronic recurrent infection. The clinical significance increasingly being recognized comparable resistance. To eradicate it necessary understand cellular mechanisms underlying development. Previous works showed was attributed reduction metabolic activities activation stringent response, SOS response toxin–antitoxin system down‐regulates transcription functions. latest research findings, however, decreased alone do confer long‐lasting phenotype active defence such efflux DNA repair required long‐term maintenance phenotypic tolerance. As tolerance‐maintenance energy‐demanding, persisters need generate maintain transmembrane proton motive force (PMF) oxidative phosphorylation. This minireview summarizes current understanding essential expression bacteria, with an emphasis on importance generation PMF enabling proper functioning persisters. How can utilized targets development anti‐persister strategies will discussed.

Язык: Английский

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Can antimicrobial blue light contribute to resistance development? Genome-wide analysis revealed aBL-protective genes in Escherichia coli

Microbiology Spectrum, Год журнала: 2023, Номер 12(1)

Опубликована: Дек. 8, 2023

ABSTRACT Antimicrobial blue light (aBL) is a promising non-antibiotic approach to fighting multidrug-resistant bacteria. However, the complete mechanism of aBL action not fully understood yet. This study contributes better understanding that response depends on many factors and it hardly possible identify predominant underlying microbial sensitivity photoinactivation. The results this provide insights into genetic changes may lead bacterial survival at higher doses, giving rise aBL-resistant strains. To our best knowledge, first concerning genome-wide mutant testing aBL. We managed 64 single-gene mutants lacked certain protective genes expressing aBL-increased sensitivity. IMPORTANCE Increasing antibiotic resistance lack new antibiotic-like compounds combat are significant problems modern medicine. development alternative therapeutic strategies extremely important. an innovative microorganisms. has multitarget mode action; however, full antibacterial requires further investigation. In addition, potential risk treatment should be considered.

Язык: Английский

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Contribution of the gyrA and waaG mutants to fluoroquinolones resistance, biofilm development, and persister cells formation in Salmonella enterica serovar Typhi

Gene, Год журнала: 2023, Номер 894, С. 147943 - 147943

Опубликована: Ноя. 11, 2023

Язык: Английский

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Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 21, 2023

ABSTRACT Aminoglycoside antibiotics display broad-spectrum activity against Gram-negative and Gram-positive bacteria by targeting their ribosomes. Herein, we have demonstrated that energy metabolism plays a crucial role in aminoglycoside tolerance, as knockout strains associated with the tricarboxylic acid cycle (TCA) electron transport chain (ETC) exhibited increased tolerance to aminoglycosides mid-exponential growth phase of Escherichia coli cells. Given uptake relies on energy-driven electrochemical potential across cytoplasmic membrane, our initial expectation was these genetic perturbations would decrease proton motive force (PMF), subsequently affecting aminoglycosides. However, results did not corroborate this assumption. We found no consistent metabolic changes, ATP levels, pH variations, or membrane differences mutant compared wild type. Additionally, intracellular concentrations fluorophore-labeled gentamicin remained similar all strains. To uncover mechanism responsible for observed strains, employed untargeted mass spectrometry quantify proteins within mutants them wild-type counterparts. Our comprehensive analysis, which encompassed protein-protein association networks functional enrichment, unveiled noteworthy upregulation linked TCA during phase, suggesting compensate perturbation increasing maintain levels. Furthermore, pathway enrichment analysis shed light local network clusters displaying downregulation were both large small ribosomal binding proteins, ribosome biogenesis, translation factor activity, biosynthesis ribonucleoside monophosphates. These findings offer plausible explanation Altogether, research has mechanisms behind paving way novel strategies combat such

Язык: Английский

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Reviewer #1 (Public Review): Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance

Опубликована: Фев. 14, 2024

Aminoglycosides, a class of antibiotics, have been in use for decades, displaying broad-spectrum activity against Gram-negative and Gram-positive bacteria. They target ribosomes disrupt protein synthesis. Although their declined due to newer antibiotics with lower toxicity, increasing drug resistance has renewed interest aminoglycosides. Herein, we demonstrated that energy metabolism plays crucial role aminoglycoside tolerance, as knockout strains deleted genes associated the tricarboxylic acid cycle (TCA) electron transport chain (ETC) exhibited increased tolerance aminoglycosides mid-exponential growth phase Escherichia coli cells. Our initial hypothesis posited genetic perturbations would lead reduction proton motive force, subsequently affecting uptake This is based on prevailing notion dependent distinctive energy-driven electrochemical potential across cytoplasmic membrane. However, our results did not support this hypothesis. Despite mutant strains, found no consistent metabolic changes, ATP levels, pH variations, or membrane differences compared wild-type strains. Additionally, intracellular concentrations fluorophore-labeled gentamicin remained similar all To uncover mechanism responsible observed employed untargeted mass spectrometry quantify proteins within these mutants them counterparts. comprehensive analysis, which encompassed protein-protein association networks functional enrichment, unveiled noteworthy upregulation linked TCA suggesting compensate perturbation by maintain levels. Furthermore, pathway enrichment analysis shed light local network clusters downregulation were both large small ribosomal binding proteins, ribosome biogenesis, translation factor activity, biosynthesis ribonucleoside monophosphates. These findings offer plausible explanation Altogether, research mechanisms behind paving way novel strategies combat such

Язык: Английский

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