Antibacterial and antibiofilm activities of ceragenins against Achromobacter species isolated from cystic fibrosis patients

Abstract

Achromobacter species, which are recognized as emerging pathogens isolated from patients with cystic fibrosis, are capable of forming biofilm in the respiratory tract in patients and innate multidrug resistance to antimicrobials. CSAs are cationic salt derivatives that mimic the activity of antimicrobial peptides and exhibit antimicrobial activity against bacteria. In this study, the in vitro activities of various ceragenins against Achromobacter-species biofilms were investigated comparatively with a conventional antibiotic (meropenem). Biofilm-formation inhibition and biofilm-adhesion inhibition were investigated on five strong biofilm-producing strains. The lowest MIC₅₀ result was obtained with CSA-13. All of the tested CSAs showed significant biofilm inhibitory activity in the manner of a time- and concentration-dependent effect. To the best of our knowledge, this is the first article to evaluate the antibacterial and antibiofilm activities of tested CSAs against Achromobacter species.

Keywords:

• Achromobacter species
• antibacterial
• biofilm
• ceragenins
• cystic fibrosis

Acknowledgments

We thank Dr. Niels Norskov Lauritsen for providing us Achromobacter species from the Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark. Also, we thank Dr. Çağla Bozkurt Güzel for providing us CSA-131-P from the Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit-Istanbul, Turkey.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by a grant from the Research Fund of The University of Istanbul (Istanbul, Turkey) Project no. 52726.

Notes on contributors

Damla Damar-Çelik

Damla Damar-Çelik was born in İstanbul, Turkey on 27 February 1992. She graduated from Istanbul University Department of Biology in June 2014. She earned her Master of Science degree in January 2018 at the University of Istanbul Department of Pharmaceutical Microbiology. Her thesis is “Investigation of the Postantibiotic effects of various antibiotics alone and in combination on Achromobacter xylosoxidans strain.” During her master of science studies, she received Erasmus grant and studied in Aarhus University Hospital Department of Clinical Microbiology as part of the Erasmus Internship Programme for 2.5 months. She studied the antibiotic resistance mechanism in Achromobacter xylosoxidans in Denmark. She is currently in her third year of her PhD in Pharmaceutical Microbiology at Istanbul University, Faculty of Pharmacy under the supervision of Prof. Dr. Berna Özbek Çelik. She studies bacterial biofilm formation, antimicrobial resistance and bacteriophages. She published some articles in academic journals and attented some conferences like the European 42nd Cystic Fibrosis Conference in Liverpool-UK and VI Congress of Macedonian Microbiologists with International participation in Ohrid-Macedonia. She has been working as a research assistant at Marmara University Faculty of Pharmacy Department of Pharmaceutical Microbiology since 2017.

Emel Mataracı-Kara

Emel Mataracı-Kara received the M.Sc. and PhD. degrees from the Istanbul University Faculty of Pharmacy, Istanbul, Turkey, in 2010 and 2016, respectively. She is still working as an Assistant Professor at the Department of Pharmaceutical Microbiology Faculty of Pharmacy Istanbul University, Istanbul, Turkey. She is the author or co-author of numerous papers in both international refereed journals and conference contributions. Her work focuses on indwelling catheter infections, bloodstream infections, biofilms, in vitro pharmacokinetics and pharmacodynamics parameters of antimicrobial cationic peptides and antibiotics alone or combinations. She has received several important recognitions to her research career, including the Drug Research Prize, and Successful Researcher Awards given by Istanbul University for her academic papers.

Paul B. Savage

Paul B. Savage received his undergraduate degree in chemistry from Brigham Young University in 1988. He completed his PhD in organic chemistry with Samuel Gellman at the University of Wisconsin in 1993. He completed NIH-funded postdoctoral training with Leo Paquette at the Ohio State University in 1995. His tenure at BYU began in 1995. He has risen through the academic ranks and is now the Reed M. Izatt Professor of Chemistry and Biochemistry. His research interests are tied to innate immune function, specifically, the discovery of structural requirements of glycolipids for stimulation of natural killer T cells and the development of non-peptide mimics of endogenous antimicrobial peptides. His research has led to over 200 papers and more than 50 issued US patents. His research has been funded by the National Institutes of Health, the National Science Foundation and by corporate sponsors.

Berna Özbek-Çelik

Berna Özbek-Çelik received her undergraduate degree in biology from İstanbul University in 1996. She completed her Master Degree in Pharmaceutical Microbiology with Prof. A. Alev Gerçeker at the University of Istanbul in 2000. She completed her Ph.D. degree in Medical Microbiology in Istanbul Universitesi Medical Faculty. Prof.Berna Özbek Çelik achieved FEMS funded postdoctoral training with Prof. Patrice Nordmann at the Paris Sud University in 2007. She has risen through the academic ranks and is now the Professor of Pharmaceutic Microbiology. Her research interests are antimicrobial compounds, antibiotic combinations effects, antibiotic resistance mechanisms, bacterial biofilms specifically, the investigation of antimicrobial catheter lock solutions, and bacteriophage therapies. Her research has led to over 60 papers. His research has been funded by the İstanbul University Scientific Research Corporation Unit and the Scientific and Technological Research Council of Turkey (TUBITAK).