Candidacidal Activity of Selected Ceragenins and Human Cathelicidin LL-37 in Experimental Settings Mimicking Infection Sites

Bonita Durnaś; Urszula Wnorowska; Katarzyna Pogoda; Piotr Deptuła; Marzena Wątek; Ewelina Piktel; Stanisław Głuszek; Xiaobo Gu; Paul B Savage; Katarzyna Niemirowicz; Robert Bucki

doi:10.1371/journal.pone.0157242

Candidacidal Activity of Selected Ceragenins and Human Cathelicidin LL-37 in Experimental Settings Mimicking Infection Sites

PLoS One. 2016 Jun 17;11(6):e0157242. doi: 10.1371/journal.pone.0157242. eCollection 2016.

Authors

Affiliations

¹ Department of Physiology, Pathophysiology and Immunology of Infection, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, Poland.
² Holy Cross Oncology Center of Kielce, Artwińskiego 3, Kielce, Poland.
³ Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, Bialystok, Poland.
⁴ Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, Kraków, Poland.
⁵ The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, Poland.
⁶ Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, United States of America.

Abstract

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.

MeSH terms

Antimicrobial Cationic Peptides / administration & dosage
Aspergillus fumigatus / drug effects
Aspergillus fumigatus / pathogenicity
Biofilms / drug effects*
Biofilms / growth & development
Candida albicans / drug effects*
Candida albicans / pathogenicity
Candidiasis / drug therapy*
Candidiasis / microbiology
Cathelicidins
Cryptococcus neoformans / drug effects
Cryptococcus neoformans / pathogenicity
Drug Resistance, Fungal / drug effects
Fluconazole / administration & dosage
Humans
Microbial Sensitivity Tests
Steroids / administration & dosage*

Substances

Antimicrobial Cationic Peptides
Steroids
ceragenin CSA-13
Fluconazole
Cathelicidins

Grants and funding

This study was conducted with the use of equipment purchased by Medical University of Białystok as part of the RPOWP 2007-2013 funding, Priority I, Axis 1.1, contract No. UDA- RPPD.01.01.00-20-001/15-00 dated 26.06.2015 [http://www.nauka.gov.pl/]) and financially supported by grants from: the National Science Centre, Poland (UMO-2012/07/B/NZ6/03504 to R. Bucki and UMO-2014/15/D/NZ6/02665 to K. Niemirowicz [https://www.ncn.gov.pl/]), and National Institutes of Health, United States of America (NHHSN272201100018I to P. B. Savage [http://www.nih.gov/]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.