Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains
Sylwia Joanna Chmielewska,
Karol Skłodowski,
Joanna Depciuch,
Piotr Deptuła,
Ewelina Piktel,
Krzysztof Fiedoruk,
Patrycja Kot,
Paulina Paprocka,
Kamila Fortunka,
Tomasz Wollny,
Przemysław Wolak,
Magdalena Parlinska-Wojtan,
Paul B. Savage,
Robert Bucki
Affiliations
Sylwia Joanna Chmielewska
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland
Karol Skłodowski
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland
Joanna Depciuch
Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland
Piotr Deptuła
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland
Ewelina Piktel
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland
Krzysztof Fiedoruk
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland
Patrycja Kot
Department of Microbiology and Immunology, Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University in Kielce, 25-365 Kielce, Poland
Paulina Paprocka
Department of Microbiology and Immunology, Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University in Kielce, 25-365 Kielce, Poland
Kamila Fortunka
Department of Microbiology and Immunology, Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University in Kielce, 25-365 Kielce, Poland
Tomasz Wollny
Holy Cross Cancer Center, Kielce, 25-734 Kielce, Poland
Przemysław Wolak
Department of Microbiology and Immunology, Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University in Kielce, 25-365 Kielce, Poland
Magdalena Parlinska-Wojtan
Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland
Paul B. Savage
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
Robert Bucki
Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, 15-222 Bialystok, Poland
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.
