Structure–Activity Study, Characterization, and Mechanism of Action of an Antimicrobial Peptoid D2 and Its d- and l-Peptide Analogues
| Autor: | Paul R. Hansen, Bimal Jana, Luca Guardabassi, Peter W. Thulstrup, Natalia Molchanova, Johannes E. Hansen, Alberto Oddo, Ines Greco, Peter Damborg |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Staphylococcus pseudintermedius
Antibiotics Pharmaceutical Science Peptide medicine.disease_cause peptoid Analytical Chemistry chemistry.chemical_compound canine infections Drug Discovery chemistry.chemical_classification 0303 health sciences biology Molecular Structure Circular Dichroism Peptoid Antimicrobial peptide 3. Good health Anti-Bacterial Agents Chemistry (miscellaneous) Pseudomonas aeruginosa Molecular Medicine medicine.symptom Methicillin-Resistant Staphylococcus aureus medicine.drug_class Microbial Sensitivity Tests Article Microbiology lcsh:QD241-441 methicillin-resistant Staphylococcus pseudintermedius 03 medical and health sciences Structure-Activity Relationship lcsh:Organic chemistry mode of action medicine Physical and Theoretical Chemistry Mode of action 030304 developmental biology Dose-Response Relationship Drug 030306 microbiology Organic Chemistry Myelin Basic Protein biology.organism_classification Peptide Fragments chemistry Mechanism of action antimicrobial Antimicrobial Cationic Peptides |
| Zdroj: | Molecules Greco, I, Hansen, J E, Jana, B, Molchanova, N, Oddo, A, Thulstrup, P W, Damborg, P P, Guardabassi, L & Hansen, P R 2019, ' Structure-activity study, characterization and mechanism of action of an antimicrobial peptoid D2 and its D-and L-peptide analogues ', Molecules, vol. 24, no. 6, 1121 . https://doi.org/10.3390/molecules24061121 Molecules, Vol 24, Iss 6, p 1121 (2019) Volume 24 Issue 6 |
| ISSN: | 1420-3049 |
| Popis: | Methicillin-resistant Staphylococcus pseudintermedius (MRSP) constitutes an emerging health problem for companion animals in veterinary medicine. Therefore, discovery of novel antimicrobial agents for treatment of Staphylococcus-associated canine infections is urgently needed to reduce use of human antibiotics in veterinary medicine. In the present work, we characterized the antimicrobial activity of the peptoid D2 against S. pseudintermedius and Pseudomonas aeruginosa, which is another common integumentary pathogen in dogs. Furthermore, we performed a structure&ndash activity relationship study of D2, which included 19 peptide/peptoid analogs. Our best compound D2D, an all d-peptide analogue, showed potent minimum inhibitory concentrations (MICs) against canine S. pseudintermedius (2&ndash 4 µ g/mL) and P. aeruginosa (4 µ g/mL) isolates as well as other selected dog pathogens (2&ndash 16 µ g/mL). Time&ndash kill assays demonstrated that D2D was able to inhibit MRSP in 30 min at 1× MIC, significantly faster than D2. Our results suggest that at high concentrations D2D is rapidly lysing the bacterial membrane while D2 is inhibiting macromolecular synthesis. We probed the mechanism of action at sub-MIC concentrations of D2, D2D, the l-peptide analog and its retro analog by a macromolecular biosynthesis assay and fluorescence spectroscopy. Our data suggest that at sub-MIC concentrations D2D is membrane inactive and primarily works by cell wall inhibition, while the other compounds mainly act on the bacterial membrane. |
| Databáze: | OpenAIRE |
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