ArticlePLoS pathogens2009
Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 105 citations in OpenAlex.
- Molecular evolution and adaptations ofFrontiers in cellular and infection microbiology · 2026Review
- Article
- The Legionella pneumophila Dot/Icm Type IV Secretion System is Structurally and Functionally Resilient in Absence of Species-specific Proteins Dis2 and Dis3.Journal of molecular biology · 2025Article
- The unique Legionella longbeachae capsule favors intracellular replication and immune evasion.PLoS pathogens · 2024Article
- Monitoring Effector Translocation with the TEM-1 Beta-Lactamase Reporter System: From Endpoint to Time Course Analysis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Legionella pneumophila Rhizoferrin Promotes Bacterial Biofilm Formation and Growth within Amoebae and Macrophages.Infection and immunity · 2023Article
- Legionella para-effectors target chromatin and promote bacterial replication.Nature communications · 2023Article
- Manipulating cell motility byJournal of translational internal medicine · 2023Article
- Legionella longbeachae effector protein RavZ inhibits autophagy and regulates phagosome ubiquitination during infection.PloS one · 2023Article
- 5' Untranslated mRNA Regions Allow Bypass of Host Cell Translation Inhibition by Legionella pneumophila.Infection and immunity · 2022Article
- Article
- Article
- TheCurrent research in microbial sciences · 2022Article
- Interfering with Autophagy: The Opposing Strategies Deployed byFrontiers in cellular and infection microbiology · 2020Review
- Type II Secretion Promotes Bacterial Growth within theInfection and immunity · 2019Article
- Viewing Legionella pneumophila Pathogenesis through an Immunological Lens.Journal of molecular biology · 2019Review
- Inhibiting bacterial secretion systems in the fight against antibiotic resistance.MedChemComm · 2019Review
- Targeting host lipid flows: Exploring new antiviral and antibiotic strategies.Cellular microbiology · 2019Review
- Identification and characterization of a large family of superbinding bacterial SH2 domains.Nature communications · 2018Article
- The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote Infection.Cell host & microbe · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters a target host cell. We used chemical genetics, a perturbation strategy that utilizes small molecule inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot activity. From a collection of more than 2,500 annotated molecules we identified specific inhibitors of effector translocation. We found that L. pneumophila effector translocation in macrophages requires host cell factors known to be involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin. Moreover, we found that L. pneumophila phagocytosis and effector translocation also specifically require the receptor protein tyrosine phosphate phosphatases CD45 and CD148. We further show that phagocytosis is required to trigger effector delivery unless intimate contact between the bacteria and the host is artificially generated. In addition, real-time analysis of effector translocation suggests that effector export is rate-limited by phagocytosis. We propose a model in which L. pneumophila utilizes phagocytosis to initiate an intimate contact event required for the translocation of pre-synthesized effector molecules. We discuss the need for host cell participation in the initial step of the infection and its implications in the L. pneumophila lifestyle. Chemical genetic screening provides a novel approach to probe the host cell functions and factors involved in host-pathogen interactions.
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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.