ArticleAntimicrobial agents and chemotherapy2012
Mechanism of action of the arylomycin antibiotics and effects of signal peptidase I inhibition.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
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- Unveiling metabolo-genomic insights of potent antitumoral and antibiotic activity inFrontiers in microbiology · 2024Article
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- New Perspectives on Escherichia coli Signal Peptidase I Substrate Specificity: Investigating Why the TasA Cleavage Site Is Incompatible with LepB Cleavage.Microbiology spectrum · 2023Article
- Using display technologies to identify macrocyclic peptide antibiotics.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Combining Signal Peptidase and Lipoprotein Processing Inhibitors Overcomes Ayr Resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2023Article
- Stretching Peptides' Potential to Target Protein-Protein Interactions.ACS central science · 2023Article
- Carrier Protein-Free Enzymatic Biaryl Coupling in Arylomycin A2 Assembly and Structure of the Cytochrome P450 AryC.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms.Frontiers in cellular and infection microbiology · 2022Article
- Bacterial Signal Peptides- Navigating the Journey of Proteins.Frontiers in physiology · 2022Review
- Emerging peptide antibiotics with therapeutic potential.Medicine in drug discovery · 2021Review
- Mapping and Exploiting the Promiscuity of OxyB toward the Biocatalytic Production of Vancomycin Aglycone Variants.ACS catalysis · 2020Article
- Venturicidin A, A Membrane-active Natural Product Inhibitor of ATP synthase Potentiates Aminoglycoside Antibiotics.Scientific reports · 2020Article
- Instructive Advances in Chemical Microbiology Inspired by Nature's Diverse Inventory of Molecules.ACS infectious diseases · 2020Review
- Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms.Nature chemistry · 2020Article
- Review
- Inhibition of Protein Secretion inAntimicrobial agents and chemotherapy · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Clinically approved antibiotics inhibit only a small number of conserved pathways that are essential for bacterial viability, and the physiological effects of inhibiting these pathways have been studied in great detail. Likewise, characterizing the effects of candidate antibiotics that function via novel mechanisms of action is critical for their development, which is of increasing importance due to the ever-growing problem of resistance. The arylomycins are a novel class of natural-product antibiotics that act via the inhibition of type I signal peptidase (SPase), which is an essential enzyme that functions as part of the general secretory pathway and is not the target of any clinically deployed antibiotic. Correspondingly, little is known about the effects of SPase inhibition or how bacteria may respond to mitigate the associated secretion stress. Using genetically sensitized Escherichia coli and Staphylococcus aureus as model organisms, we examine the activity of arylomycin as a function of its concentration, bacterial cell density, target expression levels, and bacterial growth phase. The results reveal that the activity of the arylomycins results from an insufficient flux of proteins through the secretion pathway and the resulting mislocalization of proteins. Interestingly, this has profoundly different effects on E. coli and S. aureus. Finally, we examine the activity of arylomycin in combination with distinct classes of antibiotics and demonstrate that SPase inhibition results in synergistic sensitivity when combined with an aminoglycoside.
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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.