ceragenin-csa-13 and Cystic-Fibrosis

ceragenin-csa-13 has been researched along with Cystic-Fibrosis* in 5 studies

Other Studies

5 other study(ies) available for ceragenin-csa-13 and Cystic-Fibrosis

ArticleYear
Bactericidal activities of cathelicidin LL-37 and select cationic lipids against the hypervirulent Pseudomonas aeruginosa strain LESB58.
    Antimicrobial agents and chemotherapy, 2015, Volume: 59, Issue:7

    Pseudomonas aeruginosa Liverpool epidemic strain (LES) infections in cystic fibrosis (CF) patients are associated with transmissibility and increased patient morbidity. This study was designed to assess the in vitro activities of cathelicidin LL-37 peptide (LL-37) and select cationic lipids against Pseudomonas aeruginosa LESB58 in CF sputum and in a setting mimicking the CF airway. We found that LL-37 naturally present in airway surface fluid and some nonpeptide cationic lipid molecules such as CSA-13, CSA-90, CSA-131, and D2S have significant, but broadly differing, bactericidal activities against P. aeruginosa LESB58. We observed strong inhibition of LL-37 bactericidal activity in the presence of purified bacteriophage Pf1, which is highly expressed by P. aeruginosa LES, but the activities of the cationic lipids CSA-13 and CSA-131 were not affected by this polyanionic virus. Additionally, CSA-13 and CSA-131 effectively prevent LESB58 biofilm formation, which is stimulated by Pf1 bacteriophage, DNA, or F-actin. CSA-13 and CSA-131 display strong antibacterial activities against different clinical strains of P. aeruginosa, and their activities against P. aeruginosa LESB58 and Xen5 strains were maintained in CF sputum. These data indicate that synthetic cationic lipids (mimics of natural antimicrobial peptides) are suitable for developing an effective treatment against CF lung P. aeruginosa infections, including those caused by LES strains.

    Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bacteriophage Pf1; Biofilms; Cathelicidins; Cystic Fibrosis; Humans; Lipids; Microbial Sensitivity Tests; Microscopy, Atomic Force; Models, Biological; Pregnanes; Propylamines; Pseudomonas aeruginosa; Steroids

2015
Study of the effect of antimicrobial peptide mimic, CSA-13, on an established biofilm formed by Pseudomonas aeruginosa.
    MicrobiologyOpen, 2013, Volume: 2, Issue:2

    The formation of a Pseudomonas aeruginosa biofilm, a complex structure enclosing bacterial cells in an extracellular polymeric matrix, is responsible for persistent infections in cystic fibrosis patients leading to a high rate of morbidity and mortality. The protective environment created by the tridimensional structure reduces the susceptibility of the bacteria to conventional antibiotherapy. Cationic steroid antibiotics (CSA)-13, a nonpeptide mimic of antimicrobial peptides with antibacterial activity on planktonic cultures, was evaluated for its ability to interact with sessile cells. Using confocal laser scanning microscopy, we demonstrated that the drug damaged bacteria within an established biofilm showing that penetration did not limit the activity of this antimicrobial agent against a biofilm. When biofilms were grown during exposure to shear forces and to a continuous medium flow allowing the development of robust structures with a complex architecture, CSA-13 reached the bacteria entrapped in the biofilm within 30 min. The permeabilizing effect of CSA-13 could be associated with the death of the bacteria. In static conditions, the compound did not perturb the architecture of the biofilm. This study confirms the potential of CSA-13 as a new strategy to combat persistent infections involving biofilms formed by P. aeruginosa.

    Topics: Anti-Infective Agents; Biofilms; Cystic Fibrosis; Humans; Microbial Sensitivity Tests; Microscopy, Confocal; Pseudomonas aeruginosa; Steroids

2013
Potential of ceragenin CSA-13 and its mixture with pluronic F-127 as treatment of topical bacterial infections.
    Journal of applied microbiology, 2011, Volume: 110, Issue:1

    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.. 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).. These results suggest that CSA-13 may be useful to prevent and treat topical infection.. Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.

    Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Biofilms; Cholic Acid; Cystic Fibrosis; Hemolysis; Humans; Poloxamer; Pseudomonas aeruginosa; Pseudomonas Infections; Skin Diseases, Bacterial; Staphylococcus aureus; Steroids; Surface-Active Agents

2011
In vitro activities of the novel ceragenin CSA-13, alone or in combination with colistin, tobramycin, and ciprofloxacin, against Pseudomonas aeruginosa strains isolated from cystic fibrosis patients.
    Chemotherapy, 2011, Volume: 57, Issue:6

    The rise in the rates of antibiotic resistance among Pseudomonas aeruginosa strains from cystic fibrosis (CF) patients is concerning and underscores the need for the development of novel compounds. Among them CSA-13, a cationic steroid molecule, mimics the activity of naturally occurring antimicrobial peptides.. MICs and MBCs were determined using the microbroth dilution technique. Combinations were assessed using the checkerboard technique. The bactericidal activity of CSA-13 in combination with colistin was measured using the time-kill curve method for two strains.. The MIC(90) values of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1, and 2 mg/l, respectively. The MBCs were equal to or two-fold greater than those of the MICs. With a fractional inhibitory concentration index of ≤0.5 as borderline, synergistic interactions were mostly seen with the CSA-13-colistin combination (54%). No antagonism was observed. The results of the time-kill curve analysis demonstrated rapid bactericidal activity of CSA-13 and synergism with colistin; in one strain early synergy was achieved.. CSA-13 appears to be a good candidate in the treatment of P. aeruginosa strains in CF patients. Future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.

    Topics: Ciprofloxacin; Colistin; Cystic Fibrosis; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Steroids; Tobramycin

2011
Resistance of the antibacterial agent ceragenin CSA-13 to inactivation by DNA or F-actin and its activity in cystic fibrosis sputum.
    The Journal of antimicrobial chemotherapy, 2007, Volume: 60, Issue:3

    The goal of this study was to evaluate the effects of DNA and F-actin [polyanions present in high concentration in cystic fibrosis (CF) airway fluid] on the antibacterial activities of the cationic steroid antibiotic CSA-13 and the cationic peptides LL37, WLBU2 and HB71.. Light scattering intensity was used to evaluate the aggregation of DNA and F-actin by the cationic antibacterial agents. Bacterial killing assays, atomic force microscopy, determination of MIC values and bacterial load of CF sputa were used to determine the bactericidal activity. Inhibition of nuclear factor-kappaB (NF-kappaB) translocation in human aorta endothelial cells (HAECs) was quantified as an assay of anti-inflammatory action.. CSA-13 is significantly more effective than cationic antibacterial peptides against kanamycin-resistant Pseudomonas aeruginosa and less susceptible to inactivation by DNA or F-actin. The concentration of CSA-13 sufficient to decrease the CF sputa bacteria load by approximately 90% is at least 10 times lower than that at which CSA-13 formed aggregates with DNA or F-actin. Both CSA-13 and LL37 prevent lipopolysaccharide-induced translocation of NF-kappaB in HAEC, thereby suggesting that these antibacterial molecules might prevent systemic inflammation caused by bacterial wall components.. Charge-based interactions that strongly inhibit the antibacterial activity of host cationic antibacterial peptides present in CF sputa have significantly less effect on molecules from the ceragenin family such as CSA-13 due in part to their smaller net charge and distribution of this charge over a hydrophobic scaffold. CSA molecules therefore have potential for the treatment of chronic infections and inflammation that occur in CF airways and other settings in which extracellular polyanions accumulate.

    Topics: Actins; Adult; Amino Acid Sequence; Anti-Bacterial Agents; Bacteria; Cell Line; Cystic Fibrosis; Deoxyribonuclease I; DNA; Drug Resistance, Bacterial; Electrolytes; Endothelial Cells; Erythrocytes; Hemolysis; Humans; Lipopolysaccharides; Microbial Sensitivity Tests; Microscopy, Atomic Force; Peptides; Sputum; Steroids; Teichoic Acids

2007