ArticleAntioxidants & redox signaling2018
Inhibition of Diverse DsbA Enzymes in Multi-DsbA Encoding Pathogens.
Article in Antioxidants & redox signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Drug-resistantClinical microbiology reviews · 2025Pooled it
- Repurposing loratadine to reverse colistin resistance inEmerging microbes & infections · 2026Article
- Genome-wide characterization of host factors involved in single-stranded RNA and DNA phage infection pathways.bioRxiv : the preprint server for biology · 2026Article
- Antibiotic potentiation and inhibition of cross-resistance in pathogens associated with cystic fibrosis.eLife · 2026Article
- Structural and functional specialization of Bordetella pertussis DsbA for pertussis toxin folding.Protein science : a publication of the Protein Society · 2026Article
- Unraveling the Multifunctional Therapeutic Potential of Topsentin: A Marine-derived Versatile Scaffold.Mini reviews in medicinal chemistry · 2026Review
- Unveiling the versatility of the thioredoxin framework: Insights from the structural examination ofComputational and structural biotechnology journal · 2024Article
- Fluoromethylketone-Fragment Conjugates Designed as Covalent Modifiers of EcDsbA are Atypical Substrates.ChemMedChem · 2024Article
- Recent Developments in the Inhibition of Bacterial Adhesion as Promising Anti-Virulence Strategy.International journal of molecular sciences · 2023Article
- A Buried Water Network Modulates the Activity of theAntioxidants (Basel, Switzerland) · 2023Article
- Making a chink in their armor: Current and next-generation antimicrobial strategies against the bacterial cell envelope.Advances in microbial physiology · 2023Article
- Exploring the inhibitory potential ofFrontiers in molecular biosciences · 2023Article
- Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials.ChemMedChem · 2022Article
- Article
- Identification and characterization of two drug-like fragments that bind to the same cryptic binding pocket of Burkholderia pseudomallei DsbA.Acta crystallographica. Section D, Structural biology · 2022Article
- Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases ofInternational journal of molecular sciences · 2021Article
- Antivirulence DsbA inhibitors attenuateFASEB bioAdvances · 2021Article
- Anti-Virulence Therapeutic Approaches forAntibiotics (Basel, Switzerland) · 2021Review
- A high-throughput cell-based assay pipeline for the preclinical development of bacterial DsbA inhibitors as antivirulence therapeutics.Scientific reports · 2021Article
- Structural bioinformatic analysis of DsbA proteins and their pathogenicity associated substrates.Computational and structural biotechnology journal · 2021Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsDsbA catalyzes disulfide bond formation in secreted and outer membrane proteins in bacteria. In pathogens, DsbA is a major facilitator of virulence constituting a target for antivirulence antimicrobial development. However, many pathogens encode multiple and diverse DsbA enzymes for virulence factor folding during infection. The aim of this study was to determine whether our recently identified inhibitors of Escherichia coli K-12 DsbA can inhibit the diverse DsbA enzymes found in two important human pathogens and attenuate their virulence.
resultsDsbA inhibitors from two chemical classes (phenylthiophene and phenoxyphenyl derivatives) inhibited the virulence of uropathogenic E. coli and Salmonella enterica serovar Typhimurium, encoding two and three diverse DsbA homologues, respectively. Inhibitors blocked the virulence of dsbA null mutants complemented with structurally diverse DsbL and SrgA, suggesting that they were not selective for prototypical DsbA. Structural characterization of DsbA-inhibitor complexes showed that compounds from each class bind in a similar region of the hydrophobic groove adjacent to the Cys30-Pro31-His32-Cys33 (CPHC) active site. Modeling of DsbL- and SrgA-inhibitor interactions showed that these accessory enzymes could accommodate the inhibitors in their different hydrophobic grooves, supporting our in vivo findings. Further, we identified highly conserved residues surrounding the active site for 20 diverse bacterial DsbA enzymes, which could be exploited in developing inhibitors with a broad spectrum of activity. Innovation and Conclusion: We have developed tools to analyze the specificity of DsbA inhibitors in bacterial pathogens encoding multiple DsbA enzymes. This work demonstrates that DsbA inhibitors can be developed to target diverse homologues found in bacteria. Antioxid. Redox Signal. 29, 653-666.
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