The <i>Escherichia coli</i> Envelope Stress Sensor CpxA Responds to Changes in Lipid Bilayer Properties

Keller, Rebecca; Ariöz, Candan; Hansmeier, Nicole; Stenberg-Bruzell, Filippa; Burstedt, Malin; Vikström, David; Kelly, Amélie A.; Wieslander, Åke; Daley, Daniel O.; Hunke, Sabine

doi:10.1021/acs.biochem.5b00242

Cited by 23 publications

(18 citation statements)

References 50 publications

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“…CpxRA two‐component system is a transmembrane sensor of envelope stress and is activated by a variety of insults, including misfolded proteins in the periplasm and in the cytoplasmic and outer membranes, alterations in membrane proteins, lipids, or peptidoglycan and also by many other stresses, such as pH, metals, osmolarity, adhesion, EDTA, indole, ethanol, other metabolites and PGRPs (Kashyap et al ., ; Zhou et al ., ; Hunke et al ., ; Evans et al ., ; Raivio, ; Bernal‐Cabas et al ., ; Keller et al ., ; Delhaye et al ., ). However, the exact mechanism of CpxRA activation by such a large variety of stimuli still remains elusive (Raivio, ; Delhaye et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism

Kashyap

Kuzma

Kowalczyk

et al. 2017

Molecular Microbiology

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Summary Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol, and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn2+ through influx of extracellular Zn2+) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol, and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy.

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Section: Discussionmentioning

confidence: 97%

Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism

Kashyap

Kuzma

Kowalczyk

et al. 2017

Molecular Microbiology

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“…An increase in PE levels is indicative of significant cell injury. PEs are also associated with bacterial stress responses 48 .…”

Section: Discussionmentioning

confidence: 99%

Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model

Wang

Meng

Zhang

et al. 2018

Sci Rep

184

166

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Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious comorbidities, such as dependence, tolerance, immunosuppression and gastrointestinal disorders limit their long-term use. In the current study, a morphine-murine model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the negative consequences associated with opioid use. Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo. Morphine-induced gut microbial dysbiosis exhibited distinct characteristic signatures, including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance and significant impairment in bile acids and morphine-3-glucuronide/morphine biotransformation in the gut. Moreover, expansion of Enterococcus faecalis was strongly correlated with gut dysbiosis following morphine treatment, and alterations in deoxycholic acid (DCA) and phosphatidylethanolamines (PEs) were associated with opioid-induced metabolomic changes. Collectively, these results indicate that morphine induced distinct alterations in the gut microbiome and metabolome, contributing to negative consequences associated with opioid use. Therapeutics directed at maintaining microbiome homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.

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“…The importance of proper membrane phospholipid composition for signal transduction was originally observed in vivo in PE-lacking cells for the Cpx stress response system, and our results demonstrate that the Cpx system is also activated in vivo upon modulation of CL and PG/CL contents. CpxA activity has recently been dissected in vitro (56), and the ability of CpxA (the transmembrane component of this system) to directly sense phospholipid composition changes was demonstrated. The Cpx system can affect the transcription of over 100 genes, several of them involved in lipid homeostasis (2,4,57), potentially linking Cpx activation to lipid composition remodeling.…”

Section: Discussionmentioning

confidence: 99%

Impact of Membrane Phospholipid Alterations in Escherichia coli on Cellular Function and Bacterial Stress Adaptation

Rowlett¹,

et al. 2017

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Bacteria have evolved multiple strategies to sense and rapidly adapt to challenging and ever-changing environmental conditions. The ability to alter membrane lipid composition, a key component of the cellular envelope, is crucial for bacterial survival and adaptation in response to environmental stress. However, the precise roles played by membrane phospholipids in bacterial physiology and stress adaptation are not fully elucidated. The goal of this study was to define the role of membrane phospholipids in adaptation to stress and maintenance of bacterial cell fitness. By using genetically modified strains in which the membrane phospholipid composition can be systematically manipulated, we show that alterations in major Escherichia coli phospholipids transform these cells globally. We found that alterations in phospholipids impair the cellular envelope structure and function, the ability to form biofilms, and bacterial fitness and cause phospholipid-dependent susceptibility to environmental stresses. This study provides an unprecedented view of the structural, signaling, and metabolic pathways in which bacterial phospholipids participate, allowing the design of new approaches in the investigation of lipiddependent processes involved in bacterial physiology and adaptation.IMPORTANCE In order to cope with and adapt to a wide range of environmental conditions, bacteria have to sense and quickly respond to fluctuating conditions. In this study, we investigated the effects of systematic and controlled alterations in bacterial phospholipids on cell shape, physiology, and stress adaptation. We provide new evidence that alterations of specific phospholipids in Escherichia coli have detrimental effects on cellular shape, envelope integrity, and cell physiology that impair biofilm formation, cellular envelope remodeling, and adaptability to environmental stresses. These findings hold promise for future antibacterial therapies that target bacterial lipid biosynthesis.KEYWORDS membranes, metabolism, phospholipids, physiology, stress adaptation, stress response B acteria have to cope with and adapt to a wide range of environmental conditions, such as nutrient limitation or exposure to antibiotics. Therefore, the ability to sense and quickly respond to fluctuating conditions is key for bacterial survival (1-3). Bacterial stress adaptation often requires major metabolic reprogramming that involves coordinated changes in the cell transcriptome, proteome, and metabolome, along with cellular envelope remodeling (4, 5). Escherichia coli cells consist of four compartments: the cytoplasm, the inner membrane, the periplasm, and the outer membrane. The inner and outer membranes exhibit different makeups. The inner membrane is a bilayer containing ␣-helical proteins, and more than 95% of the total lipids are phospholipids; the outer membrane is an asymmetric bilayer made of both phospholipids and

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The Escherichia coli Envelope Stress Sensor CpxA Responds to Changes in Lipid Bilayer Properties

Cited by 23 publications

References 50 publications

Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism

Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism

Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model

Impact of Membrane Phospholipid Alterations in Escherichia coli on Cellular Function and Bacterial Stress Adaptation

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