Candidacidal Activity of Selected Ceragenins and Human Cathelicidin LL-37 in Experimental Settings Mimicking Infection Sites.
Fungal infections, especially those caused by antibiotic resistant pathogens, have become a serious public health problem due to the growing number of immunocompromised patients, including those subjected to anticancer treatment or suffering from HIV infection. In this study we assessed fungicidal activity of the ceragenins CSA-13, CSA-131 and CSA-192 against four fluconazole-resistant Candida strains. We found that ceragenins activity against planktonic Candida cells was higher than activity of human LL-37 peptide and synthetic cationic peptide omiganan. Compared to LL-37 peptide, ceragenins in the presence of DNase I demonstrated an increased ability to kill DNA-induced Candida biofilm. Microscopy studies show that treatment with LL-37 or ceragenins causes Candida cells to undergo extensive surface changes indicating surface membrane damage. This conclusion was substantiated by observation of rapid incorporation of FITC-labeled CSA-13, CSA-131 or LL-37 peptide into the more lipophilic environment of the Candida membrane. In addition to activity against Candida spp., ceragenins CSA-131 and CSA-192 display strong fungicidal activity against sixteen clinical isolates including Cryptococcus neoformans and Aspergillus fumigatus. These results indicate the potential of ceragenins for future development as new fungicidal agents.
Department of Physiology, Pathophysiology and Immunology of Infection, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, Poland.|Holy Cross Oncology Center of Kielce, Artwińskiego 3, Kielce, Poland.
Bonita
B
Durnaś
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, Poland.
Urszula
U
Wnorowska
Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, Kraków, Poland.
Katarzyna
K
Pogoda
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, Poland.
Piotr
P
Deptuła
Holy Cross Oncology Center of Kielce, Artwińskiego 3, Kielce, Poland.
Marzena
M
Wątek
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, Poland.
Ewelina
E
Piktel
The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, Poland.
Stanisław
S
Głuszek
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.
Xiaobo
X
Gu
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.
Paul B
PB
Savage
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, Poland.
Katarzyna
K
Niemirowicz
Department of Physiology, Pathophysiology and Immunology of Infection, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, Poland.|Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, Poland.
Robert
R
Bucki
D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000472:pathogenicity; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000472:pathogenicity; D025141:Drug Resistance, Fungal / Q000187:drug effects; D015725:Fluconazole / Q000008:administration & dosage; D006801:Humans; D008826:Microbial Sensitivity Tests; D013256:Steroids / Q000008:administration & dosage*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D013256:Steroids; C521528:ceragenin CSA-13; D015725:Fluconazole; D054804:Cathelicidins