Potential of ceragenin CSA-13 and its mixture with pluronic F-127 as treatment of topical bacterial infections.
OBJECTIVE
Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127.


RESULTS
CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA).


CONCLUSIONS
These results suggest that CSA-13 may be useful to prevent and treat topical infection.


CONCLUSIONS
Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.
Department of Diagnostic Microbiology, Medical University of Białystok, Białystok, Poland.
K
K
Leszczyńska
A
A
Namiot
K
K
Cruz
F J
FJ
Byfield
E
E
Won
G
G
Mendez
W
W
Sokołowski
P B
PB
Savage
R
R
Bucki
P A
PA
Janmey
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D018441:Biofilms / Q000187:drug effects; D019826:Cholic Acid / Q000737:chemistry; D003550:Cystic Fibrosis / Q000382:microbiology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020442:Poloxamer; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D017192:Skin Diseases, Bacterial / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013256:Steroids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013501:Surface-Active Agents
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D013256:Steroids; D013501:Surface-Active Agents; C521528:ceragenin CSA-13; D020442:Poloxamer; D019826:Cholic Acid