Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains
| Autor: | Joanna Depciuch, Patrycja Kot, Robert Bucki, Krzysztof Fiedoruk, Przemysław Wolak, Magdalena Parlinska-Wojtan, Sylwia Chmielewska, Tomasz Wollny, Ewelina Piktel, Kamila Bożena Fortunka, Paulina Paprocka, Karol Skłodowski, Piotr Deptuła, Paul B. Savage |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Antibiotics Pharmaceutical Science MDR (multidrug-resistant) lcsh:RS1-441 02 engineering and technology Drug resistance nanosystems Article Microbiology lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound ceragenins Ceragenin medicine 0303 health sciences biology 030306 microbiology 021001 nanoscience & nanotechnology medicine.disease Antimicrobial biology.organism_classification Au NPs Hemolysis Multiple drug resistance chemistry CSA-131 0210 nano-technology Antibacterial activity Bacteria |
| Zdroj: | Pharmaceutics, Vol 13, Iss 425, p 425 (2021) Pharmaceutics Volume 13 Issue 3 |
| ISSN: | 1999-4923 |
| Popis: | Background: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. Methods: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLSb) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. Results: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. Conclusions: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH3 from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria. |
| Databáze: | OpenAIRE |
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