ArticleThe Journal of antimicrobial chemotherapy2014
Suppression of type 1 pilus assembly in uropathogenic Escherichia coli by chemical inhibition of subunit polymerization.
Article in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Chemical inhibition of MrkH-dependent activation of type 3 fimbriae synthesis and biofilm formation by Klebsiella pneumoniae.NPJ biofilms and microbiomes · 2025Article
- Prediction of SafD adhesin strong binding peptides for pilus proteins assembly suppression in the prevention ofIn silico pharmacology · 2025Article
- Polyphenols and CRISPR as Quorum Quenching Agents in Antibiotic-Resistant Foodborne Human Pathogens (Foods (Basel, Switzerland) · 2024Review
- Catheter-Associated Urinary Tract Infections: Current Challenges and Future Prospects.Research and reports in urology · 2022Review
- Identification of Two Variants of Acinetobacter baumannii Strain ATCC 17978 with Distinct Genotypes and Phenotypes.Infection and immunity · 2021Article
- Interaction with the host: the role of fibronectin and extracellular matrix proteins in the adhesion of Gram-negative bacteria.Medical microbiology and immunology · 2020Review
- The small molecule nitazoxanide selectively disrupts BAM-mediated folding of the outer membrane usher protein.The Journal of biological chemistry · 2019Article
- Inhibitors of theProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Therapeutic Approaches Targeting the Assembly and Function of Chaperone-Usher Pili.EcoSal Plus · 2019Review
- Phosphoethanolamine cellulose enhances curli-mediated adhesion of uropathogenicProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Pili Assembled by the Chaperone/Usher Pathway inEcoSal Plus · 2018Review
- Role for FimH in Extraintestinal Pathogenic Escherichia coli Invasion and Translocation through the Intestinal Epithelium.Infection and immunity · 2017Article
- Targeting Bacillosamine Biosynthesis in Bacterial Pathogens: Development of Inhibitors to a Bacterial Amino-Sugar Acetyltransferase from Campylobacter jejuni.Journal of medicinal chemistry · 2017Article
- Nitazoxanide Inhibits Pilus Biogenesis by Interfering with Folding of the Usher Protein in the Outer Membrane.Antimicrobial agents and chemotherapy · 2016Article
- Antimicrobial Drugs in Fighting against Antimicrobial Resistance.Frontiers in microbiology · 2016Review
- Novel strategy for biofilm inhibition by using small molecules targeting molecular chaperone DnaK.Antimicrobial agents and chemotherapy · 2015Article
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Authors and funding
9 authors.
Funding
Abstract
objectivesTo identify and to characterize small-molecule inhibitors that target the subunit polymerization of the type 1 pilus assembly in uropathogenic Escherichia coli (UPEC).
methodsUsing an SDS-PAGE-based assay, in silico pre-filtered small-molecule compounds were screened for specific inhibitory activity against the critical subunit polymerization step of the chaperone-usher pathway during pilus biogenesis. The biological activity of one of the compounds was validated in assays monitoring UPEC type 1 pilus biogenesis, type 1 pilus-dependent biofilm formation and adherence to human bladder epithelial cells. The time dependence of the in vivo inhibitory activity and the overall effect of the compound on UPEC growth were determined.
resultsN-(4-chloro-phenyl)-2-{5-[4-(pyrrolidine-1-sulfonyl)-phenyl]-[1,3,4]oxadiazol-2-yl sulfanyl}-acetamide (AL1) inhibited in vitro pilus subunit polymerization. In bacterial cultures, AL1 disrupted UPEC type 1 pilus biogenesis and pilus-dependent biofilm formation, and resulted in the reduction of bacterial adherence to human bladder epithelial cells, without affecting bacterial cell growth. Bacterial exposure to the inhibitor led to an almost instantaneous loss of type 1 pili.
conclusionsWe have identified and characterized a small molecule that interferes with the assembly of type 1 pili. The molecule targets the polymerization step during the subunit incorporation cycle of the chaperone-usher pathway. Our discovery provides new insight into the design and development of novel anti-virulence therapies targeting key virulence factors of bacterial pathogens.
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