Stress Reduction, Bacterial Style

Gottesman, Susan

doi:10.1128/jb.00433-17

Cited by 16 publications

(18 citation statements)

References 17 publications

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“…Likewise, both Rcs and σ E respond to additional noncanonical stressors in the cell envelope (17–19). A role for Cpx in monitoring OM lipoprotein trafficking is consistent with the current understanding that Cpx aims to protect the IM against stress (11, 65, 66). Defective OM lipoprotein trafficking is known to cause OM-targeted lipoproteins to mislocalize and accumulate in the IM where some are lethally toxic (38, 67).…”

Section: Discussionsupporting

confidence: 73%

A Stress Response Monitoring Lipoprotein Trafficking to the Outer Membrane

May

Lehman

Mitchell

et al. 2019

mBio

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Gram-negative bacteria produce lipid-anchored lipoproteins that are trafficked to their outer membrane (OM). These lipoproteins are essential components in each of the molecular machines that build the OM, including the Bam machine that assembles β-barrel proteins and the Lpt pathway that transports lipopolysaccharide. Stress responses are known to monitor Bam and Lpt function, yet no stress system has been found that oversees the fundamental process of lipoprotein trafficking. We used genetic and chemical biology approaches to induce several different lipoprotein trafficking stresses in Escherichia coli. Our results identified the Cpx two-component system as a stress response for monitoring trafficking. Cpx is activated by trafficking defects and is required to protect the cell against the consequence of the resulting stress. The OM-targeted lipoprotein NlpE acts as a sensor that allows Cpx to gauge trafficking efficiency. We reveal that NlpE signals to Cpx while it is transiting the inner membrane (IM) en route to the OM and that only a small highly conserved N-terminal domain is required for signaling. We propose that defective trafficking causes NlpE to accumulate in the IM, activating Cpx to mount a transcriptional response that protects cells. Furthermore, we reconcile this new role of NlpE in signaling trafficking defects with its previously proposed role in sensing copper (Cu) stress by demonstrating that Cu impairs acylation of lipoproteins and, consequently, their trafficking to the OM. IMPORTANCE The outer membrane built by Gram-negative bacteria such as Escherichia coli forms a barrier that prevents antibiotics from entering the cell, limiting clinical options at a time of prevalent antibiotic resistance. Stress responses ensure that barrier integrity is continuously maintained. We have identified the Cpx signal transduction system as a stress response that monitors the trafficking of lipid-anchored lipoproteins to the outer membrane. These lipoproteins are needed by every machine that builds the outer membrane. Cpx monitors just one lipoprotein, NlpE, to detect the efficiency of lipoprotein trafficking in the cell. NlpE and Cpx were previously shown to play a role in resistance to copper. We show that copper blocks lipoprotein trafficking, reconciling old and new observations. Copper is an important element in innate immunity against pathogens, and our findings suggest that NlpE and Cpx help E. coli survive the assault of copper on a key outer membrane assembly pathway.

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Section: Discussionsupporting

confidence: 73%

A Stress Response Monitoring Lipoprotein Trafficking to the Outer Membrane

May

Lehman

Mitchell

et al. 2019

mBio

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“…Finally, we wanted to use the gene expression data generated as described above to begin identifying genes involved in protecting L. reuteri against the toxicity of H 2 O 2 and HOCl, based on the simple hypothesis that genes strongly upregulated by a certain stress may be involved in protecting the cell against that stress (81). We were particularly interested in identifying genes encoding factors that protect L.…”

Section: Resultsmentioning

confidence: 99%

Complex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteri

et al. 2019

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Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of proinflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes. The pathways for H2O2 and HOCl resistance in E. coli have been well studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct but overlapping responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms. IMPORTANCE Reactive oxidants, including hydrogen peroxide and hypochlorous acid, are antimicrobial compounds produced by the immune system during inflammation. Little is known, however, about how many important types of bacteria present in the human microbiome respond to these oxidants, especially commensal and other health-associated species. We have now mapped the stress response to both H2O2 and HOCl in the intestinal lactic acid bacterium Lactobacillus reuteri.

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“…These seven genes could be classified into two categories: metalloendopeptidases (LytM, Mcp02, M6 protease) and serinetype endopeptidases (serine protease, DegS, periplasmic protease, protease II). Moreover, they could be classified based on their cellular locations: inner membrane protease, DegS (VP0432) (Gottesman, 2017); periplasmic protease (VP2032) (Baird et al, 1991); and extracellular proteases, LytM (VPA1649) (Gode-Potratz et al, 2011), Mcp02 (VPA0755), M6 protease (VP0907) (Rompikuntal et al, 2015), serine protease (VPA0449) a Gene locus number of Vibrio parahaemolyticus RIMD2210633 strain. (Chimalapati et al, 2018) and protease II (VPA1467).…”

Section: Chip-seq Data Analysis Revealed a Conserved Opar-binding Motifmentioning

confidence: 99%

Quorum-Sensing Regulator OpaR Directly Represses Seven Protease Genes in Vibrio parahaemolyticus

Chang

Lee

2020

Front. Microbiol.

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Proteases play a key role in numerous bacterial physiological events. Microbial proteases are used in the pharmaceutical industry and in biomedical applications. The genus Vibrio comprises protease-producing bacteria. Proteases transform polypeptides into shorter chains for easier utilization. They also function as a virulence factor in pathogens. The mechanism by which protease genes are regulated in Vibrio parahaemolyticus, an emerging worldwide human pathogen, however, still remains unclear. Quorum sensing is the communication system of bacteria. OpaR is the master quorumsensing regulator in V. parahaemolyticus. In the present study, quantitative reverse transcriptase-polymerase chain reaction and protease gene promoter-fusion reporter assays revealed that OpaR represses seven protease genes-three metalloprotease genes and four serine protease genes-which are involved in environmental survival and bacterial virulence. Furthermore, the electrophoresis mobility shift assay demonstrated that OpaR is bound directly to the promoter region of each of the seven protease genes. DNase I footprinting identified the sequence of these OpaR-binding sites. ChIPseq analyses revealed 435 and 835 OpaR-binding sites in the late-log and stationary phases, respectively. These OpaR-binding sequences indicated a conserved OpaRbinding motif: TATTGATAAAATTATCAATA. These results advance our understanding of the protease regulation system in V. parahaemolyticus. This study is the first to reveal the OpaR motif within V. parahaemolyticus in vivo, using ChIP-seq, and to provide a database for OpaR direct regulon.

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Stress Reduction, Bacterial Style

Cited by 16 publications

References 17 publications

A Stress Response Monitoring Lipoprotein Trafficking to the Outer Membrane

A Stress Response Monitoring Lipoprotein Trafficking to the Outer Membrane

Complex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteri

Quorum-Sensing Regulator OpaR Directly Represses Seven Protease Genes in Vibrio parahaemolyticus

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