ArticleAntimicrobial agents and chemotherapy2002
Low frequencies of resistance among Staphylococcus and Enterococcus species to the bactericidal DNA polymerase inhibitor N(3)-hydroxybutyl 6-(3'-ethyl-4'-methylanilino) uracil.
Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed.
- Article
- A unique inhibitor conformation selectively targets the DNA polymerase PolC of Gram-positive priority pathogens.Nature communications · 2025Article
- Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments.Cell chemical biology · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- The Combination of Phage Therapy and β-Lactam Antibiotics for the Effective Treatment ofInternational journal of molecular sciences · 2024Article
- Pre-Steady-State Kinetic Characterization of an Antibiotic-Resistant Mutant of Staphylococcus aureus DNA Polymerase PolC.Antimicrobial agents and chemotherapy · 2023Article
- Insight Into the Anti-staphylococcal Activity of JBC 1847 at Sub-Inhibitory Concentration.Frontiers in microbiology · 2021Article
- DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens.The Journal of antimicrobial chemotherapy · 2017Review
- Optimization of a novel potent and selective bacterial DNA helicase inhibitor scaffold from a high throughput screening hit.Bioorganic & medicinal chemistry letters · 2013Article
- Challenges of antibacterial discovery.Clinical microbiology reviews · 2011Review
- Antibacterial activity and mechanism of action of a novel anilinouracil-fluoroquinolone hybrid compound.Antimicrobial agents and chemotherapy · 2007Article
- Biological characterization of novel inhibitors of the gram-positive DNA polymerase IIIC enzyme.Antimicrobial agents and chemotherapy · 2005Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 6-anilinouracils (AUs) constitute a new class of bactericidal antibiotics selective against gram-positive (Gr(+)) organisms. The AU family of compounds specifically inhibits a novel target, replicative DNA polymerase Pol IIIC. Like other antibiotics, AUs can be expected to engender the development of resistant bacteria. We have used a representative AU and clinically relevant strains of Staphylococcus aureus and Enterococcus to determine the frequency and mechanism(s) of resistance development. The frequency of resistance was determined by using N(3)-hydroxybutyl 6-(3'-ethyl-4'-methylanilino) uracil (HBEMAU) and commercially available antibiotics at eight times the MICs. For all five Gr(+) organisms tested, the frequency of resistance to HBEMAU ranged from 1 x 10(-8) to 3 x 10(-10). The frequencies of resistance to the antibiotics tested, including rifampin, gentamicin, and ciprofloxacin, were either greater than or equal to those for HBEMAU. In order to understand the mechanism of resistance, HBEMAU-resistant organisms were isolated. MIC assays showed that the organisms had increased resistance to AU inhibitors but not to other families of antibiotics. Inhibition studies with DNA polymerases from HBEMAU-sensitive and -resistant strains demonstrated that the resistance was associated with Pol IIIC. DNA sequence analysis of the entire polC genes from both wild-type and resistant organisms revealed that the resistant organisms had a sequence change that mapped to a single amino acid codon in all strains examined.
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