ArticleAntimicrobial agents and chemotherapy2014
Small-molecule inhibitors of the pseudaminic acid biosynthetic pathway: targeting motility as a key bacterial virulence factor.
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 27 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
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- The impacts of animal agriculture on One Health-Bacterial zoonosis, antimicrobial resistance, and beyond.One health (Amsterdam, Netherlands) · 2024Review
- Investigation on the substrate specificity andChemical science · 2024Article
- Recent advances in gene-editing approaches for tackling antibiotic resistance threats: a review.Frontiers in cellular and infection microbiology · 2024Review
- Recent Advances in Understanding the Molecular Mechanisms of Multidrug Resistance and Novel Approaches of CRISPR/Cas9-Based Genome-Editing to Combat This Health Emergency.International journal of nanomedicine · 2024Review
- Thioglycosides Act as Metabolic Inhibitors of Bacterial Glycan Biosynthesis.ACS infectious diseases · 2023Article
- Association of capsular polysaccharide locus 2 with prognosis ofEmerging microbes & infections · 2022Article
- CRISPR-Cas System: A Tool to Eliminate Drug-Resistant Gram-Negative Bacteria.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Azide-Functionalized Derivatives of the Virulence-Associated Sugar Pseudaminic Acid: Chiral Pool Synthesis and Labeling of Bacteria.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- An efficient and scalable synthesis of 2,4-di-RSC advances · 2021Article
- Opportunities and Challenges of Bacterial Glycosylation for the Development of Novel Antibacterial Strategies.Frontiers in microbiology · 2021Review
- Flavodoxins as Novel Therapeutic Targets againstInternational journal of molecular sciences · 2020Review
- Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era.International journal of molecular sciences · 2020Review
- Metabolic inhibitors of bacterial glycan biosynthesis.Chemical science · 2020Article
- Polar Flagella Glycosylation inFrontiers in microbiology · 2020Article
- Survival Mechanisms ofFrontiers in microbiology · 2019Article
- Staphyloxanthin: a potential target for antivirulence therapy.Infection and drug resistance · 2019Review
- Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups.Journal of the American Chemical Society · 2018Article
- The impacts of H. pylori virulence factors on the development of gastroduodenal diseases.Journal of biomedical science · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Helicobacter pylori is motile by means of polar flagella, and this motility has been shown to play a critical role in pathogenicity. The major structural flagellin proteins have been shown to be glycosylated with the nonulosonate sugar, pseudaminic acid (Pse). This glycan is unique to microorganisms, and the process of flagellin glycosylation is required for H. pylori flagellar assembly and consequent motility. As such, the Pse biosynthetic pathway offers considerable potential as an antivirulence drug target, especially since motility is required for H. pylori colonization and persistence in the host. This report describes screening the five Pse biosynthetic enzymes for small-molecule inhibitors using both high-throughput screening (HTS) and in silico (virtual screening [VS]) approaches. Using a 100,000-compound library, 1,773 hits that exhibited a 40% threshold inhibition at a 10 μM concentration were identified by HTS. In addition, VS efforts using a 1.6-million compound library directed at two pathway enzymes identified 80 hits, 4 of which exhibited reasonable inhibition at a 10 μM concentration in vitro. Further secondary screening which identified 320 unique molecular structures or validated hits was performed. Following kinetic studies and structure-activity relationship (SAR) analysis of selected inhibitors from our refined list of 320 compounds, we demonstrated that three inhibitors with 50% inhibitory concentrations (IC50s) of approximately 14 μM, which belonged to a distinct chemical cluster, were able to penetrate the Gram-negative cell membrane and prevent formation of flagella.
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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.