ArticlePLoS pathogens2020
Cytotoxic alkyl-quinolones mediate surface-induced virulence in Pseudomonas aeruginosa.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Metal-independent effects of calprotectin on cocultures ofbioRxiv : the preprint server for biology · 2026Article
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- Iron starvation increases the production of theJournal of bacteriology · 2024Article
- A folate inhibitor exploits metabolic differences in Pseudomonas aeruginosa for narrow-spectrum targeting.Nature microbiology · 2024Article
- Alkyl quinolones mediate heterogeneous colony biofilm architecture that improves community-level survival.Journal of bacteriology · 2024Article
- Whole-Cell Biosensors for Qualitative and Quantitative Analysis of Quorum Sensing Signal Molecules and the Investigation of Quorum Quenching Agents.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A genetic switch controls Pseudomonas aeruginosa surface colonization.Nature microbiology · 2023Article
- Associational Resistance to Predation by Protists in a Mixed Species Biofilm.Applied and environmental microbiology · 2023Article
- Temporal Hierarchy and Context-Dependence of Quorum Sensing Signal inLife (Basel, Switzerland) · 2022Article
- Global Regulatory Pathways Converge To Control Expression of Pseudomonas aeruginosa Type IV Pili.mBio · 2022Article
- Pseudomonas aeruginosa clinical blood isolates display significant phenotypic variability.PloS one · 2022Article
- Sub-Inhibitory Antibiotic Exposure and Virulence inAntibiotics (Basel, Switzerland) · 2021Review
- RecombinantInfection and immunity · 2021Article
- Inhibiting quinolone biosynthesis ofChemical science · 2021Article
- A Shift in Central Metabolism Accompanies Virulence Activation in Pseudomonas aeruginosa.mBio · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Surface attachment, an early step in the colonization of multiple host environments, activates the virulence of the human pathogen P. aeruginosa. However, the downstream toxins that mediate surface-dependent P. aeruginosa virulence remain unclear, as do the signaling pathways that lead to their activation. Here, we demonstrate that alkyl-quinolone (AQ) secondary metabolites are rapidly induced upon surface association and act directly on host cells to cause cytotoxicity. Surface-induced AQ cytotoxicity is independent of other AQ functions like quorum sensing or PQS-specific activities like iron sequestration. We further show that packaging of AQs in outer-membrane vesicles (OMVs) increases their cytotoxicity to host cells but not their ability to stimulate downstream quorum sensing pathways in bacteria. OMVs lacking AQs are significantly less cytotoxic, suggesting these molecules play a role in OMV cytotoxicity, in addition to their previously characterized role in OMV biogenesis. AQ reporters also enabled us to dissect the signal transduction pathways downstream of the two known regulators of surface-dependent virulence, the quorum sensing receptor, LasR, and the putative mechanosensor, PilY1. Specifically, we show that PilY1 regulates surface-induced AQ production by repressing the AlgR-AlgZ two-component system. AlgR then induces RhlR, which can induce the AQ biosynthesis operon under specific conditions. These findings collectively suggest that the induction of AQs upon surface association is both necessary and sufficient to explain surface-induced P. aeruginosa virulence.
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Registered trials
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