ArticleInfection and immunity2007
Listeriolysin O secreted by Listeria monocytogenes into the host cell cytosol is degraded by the N-end rule pathway.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
- Synergistic Roles of InlA, InlB and LLO in the Infection of Trigeminal Ganglion Neurons by Ovine-DerivedAnimals : an open access journal from MDPI · 2026Article
- An insight into the role of branched-chain α-keto acid dehydrogenase (BKD) complex in branched-chain fatty acid biosynthesis and virulence ofJournal of bacteriology · 2024Article
- Bacteria-Based Nanoprobes for Cancer Therapy.International journal of nanomedicine · 2024Review
- Article
- Listeriolysin O: A phagosome-specific cytolysin revisited.Cellular microbiology · 2019Review
- Article
- Review
- Review
- The Listeriolysin O PEST-like Sequence Co-opts AP-2-Mediated Endocytosis to Prevent Plasma Membrane Damage during Listeria Infection.Cell host & microbe · 2018Article
- Listeriolysin O: from bazooka to Swiss army knife.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Molecular docking based screening of Listeriolysin-O for improved inhibitors.Bioinformation · 2017Article
- The arginylation branch of the N-end rule pathway positively regulates cellular autophagic flux and clearance of proteotoxic proteins.Autophagy · 2016Article
- Pharmacological Modulation of the N-End Rule Pathway and Its Therapeutic Implications.Trends in pharmacological sciences · 2015Review
- Alterations of host cell ubiquitination machinery by pathogenic bacteria.Frontiers in cellular and infection microbiology · 2015Review
- Attenuated Listeria monocytogenes: a powerful and versatile vector for the future of tumor immunotherapy.Frontiers in cellular and infection microbiology · 2014Review
- Multifaceted activity of listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes.Sub-cellular biochemistry · 2014Review
- Listeriolysin O as a strong immunogenic molecule for the development of new anti-tumor vaccines.Human vaccines & immunotherapeutics · 2013Review
- Development of a single-gene, signature-tag-based approach in combination with alanine mutagenesis to identify listeriolysin O residues critical for the in vivo survival of Listeria monocytogenes.Infection and immunity · 2012Article
- Membrane assembly of the cholesterol-dependent cytolysin pore complex.Biochimica et biophysica acta · 2012Review
- The N-end rule pathway: emerging functions and molecular principles of substrate recognition.Nature reviews. Molecular cell biology · 2011Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The intracellular pathogen Listeria monocytogenes escapes from a phagosomal compartment into the cytosol by secreting the pore-forming cytolysin listeriolysin O (LLO). During the proliferation of L. monocytogenes bacteria in the mammalian cell cytosol, the secreted LLO is targeted for degradation by the ubiquitin system. We report here that LLO is a substrate of the ubiquitin-dependent N-end rule pathway, which recognizes LLO through its N-terminal Lys residue. Specifically, we demonstrated by reverse-genetic and pharmacological methods that LLO was targeted for degradation by the N-end rule pathway in reticulocyte extracts and mouse NIH 3T3 cells and after its secretion by intracellular bacteria into the mouse cell cytosol. Replacing the N-terminal Lys of LLO with a stabilizing residue such as Val increased the in vivo half-life of LLO but did not strongly affect the intracellular growth or virulence of L. monocytogenes. Nevertheless, this replacement decreased the virulence of L. monocytogenes by nearly twofold, suggesting that a destabilizing N-terminal residue of LLO may stem from positive selection during the evolution of this and related bacteria. A double mutant strain of L. monocytogenes in which upregulated secretion of LLO was combined with a stabilizing N-terminal residue was severely toxic to infected mammalian cells, resulting in reduced intracellular growth of bacteria and an approximately 100-fold-lower level of virulence. In summary, we showed that LLO is degraded by the N-end rule pathway and that the degradation of LLO can reduce the toxicity of L. monocytogenes during infection, a property of LLO that may have been selected for its positive effects on fitness during the evolution of L. monocytogenes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.