ArticlePLoS pathogens2014
Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Peptidoglycan recognition proteins in the brain: Role in neuroinflammation and behavioral consequences.Histology and histopathology · 2026Review
- Palaeoproteomic investigation of an ancient human skeleton with abnormal deposition of dental calculus.Scientific reports · 2024Article
- A spatiotemporal drug release scaffold with antibiosis and bone regeneration for osteomyelitis.Journal of advanced research · 2023Article
- Antibacterial Activity of Rainbow Trout Plasma: In Vitro Assays and Proteomic Analysis.Animals : an open access journal from MDPI · 2023Article
- Antimicrobial Properties and Mode of Action of Cryptdin-4, a Mouse α-Defensin Regulated by Peptide Redox Structures and Bacterial Cultivation Conditions.Antibiotics (Basel, Switzerland) · 2023Article
- Bacterial virulence regulation through soluble peptidoglycan fragments sensing and response: knowledge gaps and therapeutic potential.FEMS microbiology reviews · 2023Article
- Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.Open biology · 2022Review
- Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Redox signaling through zinc activates the radiation response in Deinococcus bacteria.Scientific reports · 2021Article
- Respiratory chain components are required for peptidoglycan recognition protein-induced thiol depletion and killing in Bacillus subtilis and Escherichia coli.Scientific reports · 2021Article
- T6SS Mediated Stress Responses for Bacterial Environmental Survival and Host Adaptation.International journal of molecular sciences · 2021Review
- A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis.PLoS pathogens · 2020Article
- Formate dehydrogenase, ubiquinone, and cytochrome bd-I are required for peptidoglycan recognition protein-induced oxidative stress and killing in Escherichia coli.Scientific reports · 2020Article
- Mammary Gland Transcriptome and Proteome Modifications by Nutrient Restriction in Early Lactation Holstein Cows Challenged with Intra-Mammary Lipopolysaccharide.International journal of molecular sciences · 2019Article
- Profiling the susceptibility of Pseudomonas aeruginosa strains from acute and chronic infections to cell-wall-targeting immune proteins.Scientific reports · 2019Article
- Peptidoglycan Recognition Protein 4 Suppresses Early Inflammatory Responses toInfection and immunity · 2019Article
- Salmonella and Reactive Oxygen Species: A Love-Hate Relationship.Journal of innate immunity · 2019Review
- Detection of Shared Balancing Selection in the Absence of Trans-Species Polymorphism.Molecular biology and evolution · 2019Article
- Modulating the 3' end-DNA and the fermentation process for enhanced production and biological activity of porcine interferon-gamma.PloS one · 2019Article
- Peptidoglycan Muropeptides: Release, Perception, and Functions as Signaling Molecules.Frontiers in microbiology · 2019Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Mammalian Peptidoglycan Recognition Proteins (PGRPs) are a family of evolutionary conserved bactericidal innate immunity proteins, but the mechanism through which they kill bacteria is unclear. We previously proposed that PGRPs are bactericidal due to induction of reactive oxygen species (ROS), a mechanism of killing that was also postulated, and later refuted, for several bactericidal antibiotics. Here, using whole genome expression arrays, qRT-PCR, and biochemical tests we show that in both Escherichia coli and Bacillus subtilis PGRPs induce a transcriptomic signature characteristic of oxidative stress, as well as correlated biochemical changes. However, induction of ROS was required, but not sufficient for PGRP killing. PGRPs also induced depletion of intracellular thiols and increased cytosolic concentrations of zinc and copper, as evidenced by transcriptome changes and supported by direct measurements. Depletion of thiols and elevated concentrations of metals were also required, but by themselves not sufficient, for bacterial killing. Chemical treatment studies demonstrated that efficient bacterial killing can be recapitulated only by the simultaneous addition of agents leading to production of ROS, depletion of thiols, and elevation of intracellular metal concentrations. These results identify a novel mechanism of bacterial killing by innate immunity proteins, which depends on synergistic effect of oxidative, thiol, and metal stress and differs from bacterial killing by antibiotics. These results offer potential targets for developing new antibacterial agents that would kill antibiotic-resistant bacteria.
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