Ceragenin CSA-13 exhibits antimicrobial activity against cariogenic and periodontopathic bacteria.
BACKGROUND
Ceragenin CSA-13 is a bile-acid-based mimic of endogenous antimicrobial peptides and shares a mechanism of action with many of these antimicrobial agents. Because CSA-13 is not peptide based, it is not a substrate for the proteases that are found in the oral cavity, which are capable of degrading antimicrobial peptides. Furthermore, the simplicity of the ceragenins makes them easier to prepare and purify than antimicrobial peptides. In this study, we examined the antimicrobial activities of CSA-13 against oral pathogens and found that this compound was bactericidal against all of the strains tested.


METHODS
The strains used were isolates of Streptococcus mutans and Porphyromonas species. Minimum inhibitory concentrations (MIC) were determined using agar dilution methods. In susceptibility testing, viable counts were determined after incubation with CSA-13.


RESULTS
CSA-13 was potent against all 23 strains tested with MICs of 1-8 microg/ml for S. mutans and 1-16 microg/ml for 24 strains of the genus Porphyromonas. The MIC(50) was 2 and the MIC(90) was 8 mug/ml for S. mutans. MIC ranges for protease-positive P. gingivalis and P. cangingivalis were 2-16 microg/ml, and 1-2 microg/ml for protease-negative P. circumdentaria. CSA-13 interacted with lipopolysaccharide-sensitized erythrocytes at a concentration of 5.0-20.0 microg/ml.


CONCLUSIONS
CSA-13 displays broad-spectrum activity against cariogenic and periodontopathic bacteria. CSA-13 was effective against protease-positive Porphyromonas. It was shown to bind to erythrocytes coated with lipopolysaccharide and lipoteichoic acid from diverse bacterial strains. These results suggest that CSA-13 may be useful for the prevention and treatment of oral microbial diseases.
Isogai
E
E
Department of Disease Control and Molecular Epidemiology, Health Sciences University of Hokkaido, Hokkaido, Japan. emiko@hoku-iryo-u.ac.jp
Isogai
H
H
Takahashi
K
K
Okumura
K
K
Savage
P B
PB
D000595:Amino Acid Sequence; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D003773:Dental Plaque / Q000382:microbiology; D052978:Disk Diffusion Antimicrobial Tests; D006801:Humans; D008969:Molecular Sequence Data; D010510:Periodontal Diseases / Q000382:microbiology; D017861:Porphyromonas / Q000187:drug effects*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013295:Streptococcus mutans / Q000187:drug effects*
D000891:Anti-Infective Agents, Local; D023181:Antimicrobial Cationic Peptides; D013256:Steroids; C521528:ceragenin CSA-13