Expanding the Spectrum of Antibiotics Capable of Killing Multidrug-Resistant Staphylococcus aureus and Pseudomonas aeruginosa
| Autor: | Anh K. Lam, Robert E. Brennan, Jennifer Pusavat, Charles V. Rice, Hannah Panlilio, Cassandra L. Wouters, Erika L. Moen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Penicillin binding proteins medicine.drug_class Antibiotics Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Biochemistry Article Microbiology Structure-Activity Relationship Antibiotic resistance Drug Discovery Medicine Humans General Pharmacology Toxicology and Pharmaceutics Pharmacology biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry business.industry Pseudomonas aeruginosa Organic Chemistry Interleukin-8 Pathogenic bacteria biology.organism_classification 0104 chemical sciences Anti-Bacterial Agents Multiple drug resistance 010404 medicinal & biomolecular chemistry HEK293 Cells Staphylococcus aureus Molecular Medicine business Bacteria |
| Zdroj: | ChemMedChem |
| ISSN: | 1860-7187 |
| Popis: | Infections from antibiotic resistant Staphylococcus aureus and Pseudomonas aeruginosa are a serious threat because reduced antibiotic efficacy complicates treatment decisions and prolongs the disease state in many patients. To expand the arsenal of treatments against antimicrobial resistant (AMR) pathogens, 600-Da branched polyethylenimine (BPEI) can overcome antibiotic resistance mechanisms and potentiate β-lactam antibiotics against Gram-positive bacteria. BPEI binds cell wall teichoic acids and disables resistance factors from penicillin binding proteins PBP2a and PBP4. The present study describes a new mechanism of action for BPEI potentiation of antibiotics generally regarded as agents effective against Gram-positive pathogens but not Gram-negative bacteria. 600-Da BPEI is able to reduce the barriers to drug influx and facilitate the uptake of a non-β-lactam co-drug, erythromycin, that targets the intracellular machinery. Also, BPEI can suppress production of the cytokine interleukin IL-8 by human epithelial keratinocytes. This enables BPEI to function as a broad-spectrum antibiotic potentiator which expands the opportunities to improve drug design, antibiotic development, and therapeutic approaches against pathogenic bacteria, especially for wound care. |
| Databáze: | OpenAIRE |
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