ArticleAntimicrobial agents and chemotherapy2014
Mutations in the Pseudomonas aeruginosa needle protein gene pscF confer resistance to phenoxyacetamide inhibitors of the type III secretion system.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Topical formulation of repurposed FDA-approved compounds inhibits Pseudomonas aeruginosa ExoU and improves corneal infection outcomes.PLoS pathogens · 2026Article
- Multiple virulence attenuating strategies against Pseudomonas aeruginosa: Natural, synthetic, and synergistic approaches.World journal of microbiology & biotechnology · 2026Review
- Neutralizing human monoclonal antibodies that target the PcrV component of the type III secretion system ofeLife · 2026Article
- Using next generation antimicrobials to target the mechanisms of infection.npj antimicrobials and resistance · 2023Review
- Five Plant Natural Products Are Potential Type III Secretion System Inhibitors to Effectively Control Soft-Rot Disease Caused byFrontiers in microbiology · 2022Article
- Pseudomonas aeruginosa Antivirulence Strategies: Targeting the Type III Secretion System.Advances in experimental medicine and biology · 2022Article
- Developing Cyclic Peptomers as Broad-Spectrum Type III Secretion System Inhibitors in Gram-Negative Bacteria.Antimicrobial agents and chemotherapy · 2021Article
- Review
- Molecular Targets and Strategies for Inhibition of the Bacterial Type III Secretion System (T3SS); Inhibitors Directly Binding to T3SS Components.Biomolecules · 2021Review
- Attenuation ofVirulence · 2020Article
- A Structure-Function-Inhibition Analysis of theJournal of bacteriology · 2020Article
- Novel Noncompetitive Type Three Secretion System ATPase Inhibitors Shut DownBiochemistry · 2020Article
- Review of PotentialJournal of fungi (Basel, Switzerland) · 2020Review
- On the road to structure-based development of anti-virulence therapeutics targeting the type III secretion system injectisome.MedChemComm · 2019Review
- Tanshinones: First-in-Class Inhibitors of the Biogenesis of the Type 3 Secretion System Needle ofACS central science · 2019Article
- Transcriptional responses of Xanthomonas oryzae pv. oryzae to type III secretion system inhibitor ortho-coumaric acid.BMC microbiology · 2019Article
- Small Molecule Inhibitors Specifically Targeting the Type III Secretion System ofInternational journal of molecular sciences · 2019Article
- Promises and Challenges of the Type Three Secretion System Injectisome as an Antivirulence Target.EcoSal Plus · 2019Review
- Discovery of Ethyl 2-Nitro-3-Arylacrylates Molecules as T3SS Inhibitor Reducing the Virulence of Plant Pathogenic BacteriaFrontiers in microbiology · 2019Article
- Emerging therapies against infections withF1000Research · 2019Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The type III secretion system (T3SS) is a clinically important virulence mechanism in Pseudomonas aeruginosa that secretes and translocates effector toxins into host cells, impeding the host's rapid innate immune response to infection. Inhibitors of T3SS may be useful as prophylactic or adjunctive therapeutic agents to augment the activity of antibiotics in P. aeruginosa infections, such as pneumonia and bacteremia. One such inhibitor, the phenoxyacetamide MBX 1641, exhibits very responsive structure-activity relationships, including striking stereoselectivity, in its inhibition of P. aeruginosa T3SS. These features suggest interaction with a specific, but unknown, protein target. Here, we identify the apparent molecular target by isolating inhibitor-resistant mutants and mapping the mutation sites by deep sequencing. Selection and sequencing of four independent mutants resistant to the phenoxyacetamide inhibitor MBX 2359 identified the T3SS gene pscF, encoding the needle apparatus, as the only locus of mutations common to all four strains. Transfer of the wild-type and mutated alleles of pscF, together with its chaperone and cochaperone genes pscE and pscG, to a ΔpscF P. aeruginosa strain demonstrated that each of the single-codon mutations in pscF is necessary and sufficient to provide secretion and translocation that is resistant to a variety of phenoxyacetamide inhibitor analogs but not to T3SS inhibitors with different chemical scaffolds. These results implicate the PscF needle protein as an apparent new molecular target for T3SS inhibitor discovery and suggest that three other chemically distinct T3SS inhibitors interact with one or more different targets or a different region of PscF.
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