ArticleAntimicrobial agents and chemotherapy2016
Nitazoxanide Inhibits Pilus Biogenesis by Interfering with Folding of the Usher Protein in the Outer Membrane.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- β-Barrel Assembly Machinery (BAM) Complex as Novel Antibacterial Drug Target.Molecules (Basel, Switzerland) · 2023Review
- The Role of Outer Membrane Proteins in UPEC Antimicrobial Resistance: A Systematic Review.Membranes · 2022Review
- Antibiofilm agents with therapeutic potential against enteroaggregative Escherichia coli.PLoS neglected tropical diseases · 2022Article
- Catheter-Associated Urinary Tract Infections: Current Challenges and Future Prospects.Research and reports in urology · 2022Review
- DsbA is a redox-switchable mechanical chaperone.Chemical science · 2021Article
- Possible drugs for the treatment of bacterial infections in the future: anti-virulence drugs.The Journal of antibiotics · 2021Review
- Chaperone-tip adhesin complex is vital for synergistic activation of CFA/I fimbriae biogenesis.PLoS pathogens · 2020Article
- Thiazoles, Their Benzofused Systems, and Thiazolidinone Derivatives: Versatile and Promising Tools to Combat Antibiotic Resistance.Journal of medicinal chemistry · 2020Review
- Amixicile: A Concept Therapeutic for Treatment of Chronic Anaerobic Infections.British journal of gastroenterology · 2020Article
- Review
- The small molecule nitazoxanide selectively disrupts BAM-mediated folding of the outer membrane usher protein.The Journal of biological chemistry · 2019Article
- Therapeutic Approaches Targeting the Assembly and Function of Chaperone-Usher Pili.EcoSal Plus · 2019Review
- Pili Assembled by the Chaperone/Usher Pathway inEcoSal Plus · 2018Review
- The Bacteriology and Its Virulence Factors in Neonatal Infections: Threats to Child Survival Strategies.Journal of pathogens · 2018Article
- Amixicile, a novel strategy for targeting oral anaerobic pathogens.Scientific reports · 2017Article
- Small Molecules That Sabotage Bacterial Virulence.Trends in pharmacological sciences · 2017Review
- Invasion of Host Cells and Tissues by Uropathogenic Bacteria.Microbiology spectrum · 2016Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Many bacterial pathogens assemble surface fibers termed pili or fimbriae that facilitate attachment to host cells and colonization of host tissues. The chaperone/usher (CU) pathway is a conserved secretion system that is responsible for the assembly of virulence-associated pili by many different Gram-negative bacteria. Pilus biogenesis by the CU pathway requires a dedicated periplasmic chaperone and an integral outer membrane (OM) assembly and secretion platform termed the usher. Nitazoxanide (NTZ), an antiparasitic drug, was previously shown to inhibit the function of aggregative adherence fimbriae and type 1 pili assembled by the CU pathway in enteroaggregativeEscherichia coli, an important causative agent of diarrhea. We show here that NTZ also inhibits the function of type 1 and P pili from uropathogenicE. coli(UPEC). UPEC is the primary causative agent of urinary tract infections, and type 1 and P pili mediate colonization of the bladder and kidneys, respectively. By analysis of the different stages of the CU pilus biogenesis pathway, we show that treatment of bacteria with NTZ causes a reduction in the number of usher molecules in the OM, resulting in a loss of pilus assembly on the bacterial surface. In addition, we determine that NTZ specifically prevents proper folding of the usher β-barrel domain in the OM. Our findings demonstrate that NTZ is a pilicide with a novel mechanism of action and activity against diverse CU pathways. This suggests that further development of the NTZ scaffold may lead to new antivirulence agents that target the usher to prevent pilus assembly.
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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.